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Maduri VD, Eresha J, Dulani S, Pujitha W. Association of fatty liver with serum gamma-glutamyltransferase and uric acid in obese children in a tertiary care centre. BMC Pediatr 2025; 25:144. [PMID: 40011867 PMCID: PMC11863752 DOI: 10.1186/s12887-025-05484-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 02/04/2025] [Indexed: 02/28/2025] Open
Abstract
BACKGROUND Obesity among the young is an emerging health problem with many metabolic changes including liver damage. Our objective was to investigate the association of fatty liver with serum uric acid (UA) and gamma-glutamyltransferase (GGT) in a cohort of obese children in Sri Lanka. METHODS A cross-sectional analytical study was conducted among 5-15-year-old obese children (based on WHO 2007 standards). After a 12-hour overnight fast, blood was drawn for glucose, lipid profile, alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin, UA and GGT. Height, weight, waist circumference, blood pressure and fat mass were measured. Ultrasound scan of abdomen was performed to determine fatty liver. RESULTS We studied 146 obese children with a mean age (SD) 9.86 (2.1) years. The fatty liver group showed significantly elevated levels (p < 0.05) of UA, oral glucose tolerance test (OGTT), triglycerides (TG), AST, ALT, GGT, insulin resistance (HOMA-IR) and a reduced AST/ALT ratio, compared to the non-fatty liver group. Chi square test showed statistically significant associations between fatty liver and AST, ALT, AST/ALT ratio, HOMA-IR, UA and GGT. With existing cut offs, GGT (> 30 U/L) and UA (> 330 µmol/L) the sensitivity and specificity of GGT in predicting fatty liver was 26.9% and 94.1% respectively while for UA it was 38.5% and 83.8% respectively. A cut-off value of 18.5 U/L (sensitivity 76.9% and specificity 52.9%) for GGT, 277µmol/L (sensitivity 70.5% and specificity 57.4%) for UA, 27.5 U/L (sensitivity 70.5%, specificity 51.5%) for AST, 21.5 U/L (sensitivity 80.8% and specificity 61.8%) for ALT, a ratio of 0.99 (sensitivity 77.9% and specificity 55.1%) for AST/ALT and 2.02 (sensitivity 73.2%, specificity 58.5%) for HOMA-IR predicted fatty liver. CONCLUSION GGT and UA are associated with fatty liver and these biomarkers can be used to predict fatty liver disease.
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Affiliation(s)
- Vidanapathirana Dinesha Maduri
- Department of Chemical Pathology, Lady Ridgeway Hospital, Colombo, Sri Lanka.
- Department of Pathology, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka.
| | - Jasinge Eresha
- Department of Chemical Pathology, Lady Ridgeway Hospital, Colombo, Sri Lanka
| | - Samaranayake Dulani
- Department of Community Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
| | - Wickramasinghe Pujitha
- Department of Paediatrics, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
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He F, Liu J, Huang Y, Chen L, Rizi EP, Zhang K, Ke L, Loh TP, Niu M, Peng WK. Nutritional load in post-prandial oxidative stress and the pathogeneses of diabetes mellitus. NPJ Sci Food 2024; 8:41. [PMID: 38937488 PMCID: PMC11211471 DOI: 10.1038/s41538-024-00282-x] [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: 07/08/2023] [Accepted: 06/14/2024] [Indexed: 06/29/2024] Open
Abstract
Diabetes mellitus affected more than 500 million of people globally, with an annual mortality of 1.5 million directly attributable to diabetic complications. Oxidative stress, in particularly in post-prandial state, plays a vital role in the pathogenesis of the diabetic complications. However, oxidative status marker is generally poorly characterized and their mechanisms of action are not well understood. In this work, we proposed a new framework for deep characterization of oxidative stress in erythrocytes (and in urine) using home-built micro-scale NMR system. The dynamic of post-prandial oxidative status (against a wide variety of nutritional load) in individual was assessed based on the proposed oxidative status of the red blood cells, with respect to the traditional risk-factors such as urinary isoprostane, reveals new insights into our understanding of diabetes. This new method can be potentially important in drafting guidelines for sub-stratification of diabetes mellitus for clinical care and management.
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Affiliation(s)
- Fangzhou He
- Songshan Lake Materials Laboratory, Dongguan, China
| | - Junshi Liu
- Dongguan Institute of Technology, Dongguan, China
| | | | - Lan Chen
- BioSyM, SMART Centre, Singapore, Singapore
| | | | - Ke Zhang
- Songshan Lake Materials Laboratory, Dongguan, China
| | - Lijing Ke
- School of Food Science and Nutrition, University of Leeds, Leeds, UK
| | - Tze Ping Loh
- National University of Health System, Singapore, Singapore
| | - Meng Niu
- Department of Interventional Radiology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Weng Kung Peng
- Songshan Lake Materials Laboratory, Dongguan, China.
- BioSyM, SMART Centre, Singapore, Singapore.
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Vakilpour A, Amini-Salehi E, Soltani Moghadam A, Keivanlou MH, Letafatkar N, Habibi A, Hashemi M, Eslami N, Zare R, Norouzi N, Delam H, Joukar F, Mansour-Ghanaei F, Hassanipour S, Samethadka Nayak S. The effects of gut microbiome manipulation on glycemic indices in patients with non-alcoholic fatty liver disease: a comprehensive umbrella review. Nutr Diabetes 2024; 14:25. [PMID: 38729941 PMCID: PMC11087547 DOI: 10.1038/s41387-024-00281-7] [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: 09/17/2023] [Revised: 03/26/2024] [Accepted: 04/10/2024] [Indexed: 05/12/2024] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a significant risk factor for non-alcoholic fatty liver disease (NAFLD). Increased fasting blood sugar (FBS), fasting insulin (FI), and insulin resistance (HOMA-IR) are observed in patients with NAFLD. Gut microbial modulation using prebiotics, probiotics, and synbiotics has shown promise in NAFLD treatment. This meta-umbrella study aimed to investigate the effects of gut microbial modulation on glycemic indices in patients with NAFLD and discuss potential mechanisms of action. METHODS A systematic search was conducted in PubMed, Web of Science, Scopus, and Cochrane Library until March 2023 for meta-analyses evaluating the effects of probiotics, prebiotics, and synbiotics on patients with NAFLD. Random-effect models, sensitivity analysis, and subgroup analysis were employed. RESULTS Gut microbial therapy significantly decreased HOMA-IR (ES: -0.41; 95%CI: -0.52, -0.31; P < 0.001) and FI (ES: -0.59; 95%CI: -0.77, -0.41; P < 0.001). However, no significant effect was observed on FBS (ES: -0.17; 95%CI: -0.36, 0.02; P = 0.082). Subgroup analysis revealed prebiotics had the most potent effect on HOMA-IR, followed by probiotics and synbiotics. For FI, synbiotics had the most substantial effect, followed by prebiotics and probiotics. CONCLUSION Probiotics, prebiotics, and synbiotics administration significantly reduced FI and HOMA-IR, but no significant effect was observed on FBS.
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Affiliation(s)
| | - Ehsan Amini-Salehi
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | | | - Mohammad-Hossein Keivanlou
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
- Student Research Committee, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Negin Letafatkar
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
- Student Research Committee, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Arman Habibi
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
- Student Research Committee, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Mohammad Hashemi
- Student Research Committee, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Negar Eslami
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Reza Zare
- Student Research Committee, Larestan University of Medical Sciences, Larestan, Iran
| | - Naeim Norouzi
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Hamed Delam
- Student Research Committee, Larestan University of Medical Sciences, Larestan, Iran
| | - Farahnaz Joukar
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Fariborz Mansour-Ghanaei
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Soheil Hassanipour
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran.
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Yin X, Li YS, Ye SZ, Zhang T, Zhang YW, Xi Y, Tang HB. Promotion Effect of Coexposure to a High-Fat Diet and Nano-Diethylnitrosamine on the Progression of Fatty Liver Malignant Transformation into Liver Cancer. Int J Mol Sci 2023; 24:14162. [PMID: 37762463 PMCID: PMC10531889 DOI: 10.3390/ijms241814162] [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: 08/25/2023] [Revised: 09/09/2023] [Accepted: 09/12/2023] [Indexed: 09/29/2023] Open
Abstract
Overconsumption of high-fat foods increases the risk of fatty liver disease (FLD) and liver cancer with long pathogenic cycles. It is also known that the intake of the chemical poison nitrosamine and its nanopreparations can promote the development of liver injuries, such as FLD, and hepatic fibrosis, and significantly shorten the formation time of the liver cancer cycle. The present work confirmed that the coexposure of a high-fat diet (HFD) and nano-diethylnitrosamine (nano-DEN) altered the tumor microenvironment and studied the effect of this coexposure on the progression of fatty liver malignant transformation into liver cancer. Gene transcriptomics and immunostaining were used to evaluate the tumor promotion effect of the coexposure in mice. After coexposure treatment, tumor nodules were obviously increased, and inflammation levels were elevated. The liver transcriptomics analysis showed that the expression levels of inflammatory, fatty, and fibrosis-related factors in the coexposed group were increased in comparison with the nano-DEN- and high-fat-alone groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that coexposure aggravated the high expression of genes related to the carcinomatous pathway and accelerated the formation of the tumor microenvironment. The immunohistochemical staining results showed that the coexposure significantly increased the abnormal changes in proteins related to inflammation, proliferation, aging, and hypoxia in mouse liver tissues. The coexposure of high fat and nano-DEN aggravated the process of steatosis and carcinogenesis. In conclusion, the habitual consumption of pickled foods containing nitrosamines in a daily HFD significantly increases the risk of liver pathology lesions progressing from FLD to liver cancer.
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Affiliation(s)
- Xin Yin
- Lab of Hepatopharmacology and Ethnopharmacology, School of Pharmaceutical Sciences, South-Central Minzu University, No. 182, Minyuan Road, Wuhan 430074, China; (X.Y.); (Y.-S.L.); (T.Z.); (Y.-W.Z.)
| | - Yu-Sang Li
- Lab of Hepatopharmacology and Ethnopharmacology, School of Pharmaceutical Sciences, South-Central Minzu University, No. 182, Minyuan Road, Wuhan 430074, China; (X.Y.); (Y.-S.L.); (T.Z.); (Y.-W.Z.)
| | - Sha-Zhou Ye
- Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, No. 818 Fenghua Road, Jiangbei District, Ningbo 315211, China;
| | - Ting Zhang
- Lab of Hepatopharmacology and Ethnopharmacology, School of Pharmaceutical Sciences, South-Central Minzu University, No. 182, Minyuan Road, Wuhan 430074, China; (X.Y.); (Y.-S.L.); (T.Z.); (Y.-W.Z.)
| | - Yi-Wen Zhang
- Lab of Hepatopharmacology and Ethnopharmacology, School of Pharmaceutical Sciences, South-Central Minzu University, No. 182, Minyuan Road, Wuhan 430074, China; (X.Y.); (Y.-S.L.); (T.Z.); (Y.-W.Z.)
| | - Yang Xi
- Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, No. 818 Fenghua Road, Jiangbei District, Ningbo 315211, China;
| | - He-Bin Tang
- Lab of Hepatopharmacology and Ethnopharmacology, School of Pharmaceutical Sciences, South-Central Minzu University, No. 182, Minyuan Road, Wuhan 430074, China; (X.Y.); (Y.-S.L.); (T.Z.); (Y.-W.Z.)
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Anaya-Morua W, Villafan-Bernal JR, Ramírez-Moreno E, García-Ortiz H, Martínez-Portilla RJ, Contreras-Cubas C, Martínez-Hernández A, Centeno-Cruz F, Pedroza-Montoya FE, Orozco L, Barajas-Olmos F. Total Antioxidant Capacity in Obese and Non-Obese Subjects and Its Association with Anthropo-Metabolic Markers: Systematic Review and Meta-Analysis. Antioxidants (Basel) 2023; 12:1512. [PMID: 37627507 PMCID: PMC10451178 DOI: 10.3390/antiox12081512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 07/26/2023] [Accepted: 07/26/2023] [Indexed: 08/27/2023] Open
Abstract
The total antioxidant capacity (TAC) has been related to the development of and complications associated with chronic diseases, but its importance during obesity is not entirely clear. We conducted a systematic review and meta-analysis to clarify whether there are differences or similarities in the TAC between subjects with obesity (SO) and subjects with normal weight (NW). Following the recommendations of PRISMA and Cochrane, we performed a systematic search in the PubMed, Scopus, Web of Science, Cochrane, and PROSPERO databases, identifying 1607 studies. Among these, 22 studies were included in the final analysis, comprising 3937 subjects (1665 SO and 2272 NW) in whom serum TAC was measured, and from these 19,201 subjects, the correlation of serum TAC with anthropo-metabolic parameters was also estimated. The Newcastle-Ottawa method was used for the evaluation of the risk of bias. Using a random-effect model (REM), TAC was reduced in SO independently of age (SMD, -0.86; 95% CI -1.38 to -0.34; p = 0.0012), whereas malondialdehyde (SMD, 1.50; 95% CI 0.60 to 2.41), oxidative stress index (SMD, 1.0; 95% CI 0.16 to 1.84), and total oxidant status (SMD, 0.80; 0.22 to 1.37) were increased. There were seven significant pooled correlations of TAC with anthropometric and metabolic parameters: weight (r = -0.17), hip circumference (r= -0.11), visceral adipose index (r = 0.29), triglycerides (r = 0.25), aspartate aminotransferase (r = 0.41), alanine aminotransferase (r = 0.38), and uric acid (r = 0.53). Our results confirm a decrease in TAC and an increase in markers of oxidative stress in SO and underpin the importance of these serum biomarkers in obesity.
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Affiliation(s)
- Wendoline Anaya-Morua
- Academic Area of Medicine, Interdisciplinary Research Center, Institute of Health Sciences, Autonomous University of the State of Hidalgo, Pachuca 42160, Mexico;
| | - José Rafael Villafan-Bernal
- Investigador por México, Consejo Nacional de Humanidades, Ciencia y Tecnología (CONAHCYT), Mexico City 03940, Mexico;
- Iberoamerican Research Network in Obstetrics, Gynecology and Translational Medicine, Mexico City 42160, Mexico; (R.J.M.-P.); (F.E.P.-M.)
- Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City 14610, Mexico; (H.G.-O.); (C.C.-C.); (A.M.-H.); (F.C.-C.)
| | - Esther Ramírez-Moreno
- Academic Area of Nutrition, Interdisciplinary Research Center, Institute of Health Sciences, Autonomous University of the State of Hidalgo, Pachuca 42184, Mexico;
| | - Humberto García-Ortiz
- Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City 14610, Mexico; (H.G.-O.); (C.C.-C.); (A.M.-H.); (F.C.-C.)
| | - Raigam Jafet Martínez-Portilla
- Iberoamerican Research Network in Obstetrics, Gynecology and Translational Medicine, Mexico City 42160, Mexico; (R.J.M.-P.); (F.E.P.-M.)
- Clinical Research Branch, Evidence-Based Medicine Department, National Institute of Perinatology, Mexico City 11000, Mexico
| | - Cecilia Contreras-Cubas
- Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City 14610, Mexico; (H.G.-O.); (C.C.-C.); (A.M.-H.); (F.C.-C.)
| | - Angélica Martínez-Hernández
- Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City 14610, Mexico; (H.G.-O.); (C.C.-C.); (A.M.-H.); (F.C.-C.)
| | - Federico Centeno-Cruz
- Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City 14610, Mexico; (H.G.-O.); (C.C.-C.); (A.M.-H.); (F.C.-C.)
| | - Florencia Estefana Pedroza-Montoya
- Iberoamerican Research Network in Obstetrics, Gynecology and Translational Medicine, Mexico City 42160, Mexico; (R.J.M.-P.); (F.E.P.-M.)
| | - Lorena Orozco
- Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City 14610, Mexico; (H.G.-O.); (C.C.-C.); (A.M.-H.); (F.C.-C.)
| | - Francisco Barajas-Olmos
- Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City 14610, Mexico; (H.G.-O.); (C.C.-C.); (A.M.-H.); (F.C.-C.)
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Barişik V, Korkmaz H, Çekdemir Y, Torlak D, Aktuğ H, Yavaşoğlu A, Erbaş O. THE THERAPEUTIC EFFECT OF ALLOPURINOL IN FATTY LIVER DISEASE IN RATS. ACTA ENDOCRINOLOGICA (BUCHAREST, ROMANIA : 2005) 2023; 19:155-162. [PMID: 37908883 PMCID: PMC10614584 DOI: 10.4183/aeb.2023.155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/02/2023]
Abstract
Background Hyperuricemia is associated with non-alcoholic fatty liver disease (NAFLD). Aim We therefore aimed at evaluating the influence of allopurinol on the course of NAFLD in rats. Study Design We divided 21 mature albino Sprague Dawley rats into three groups: controls (n = 7, normal diet for 12 weeks); NAFLD rat models (by feeding water containing 30% fructose for first 8 weeks) treated with allopurinol subsequently for the next 4 weeks (n = 7); and similar case treated with placebo (saline) subsequently for the next 4 weeks (n = 7). Methods We compared the histopathological scores, IL-1 and IL-2 immunoexpression levels across the groups. Liver histopathological score was determined by observing the steatosis (the percentage of liver cells containing fat): <25% = 1+, 25% - 50% = 2+, 51% - 75% = 3+, >75% = 4+; inflammation and necrosis: 1 focus per low-power field = 1+; and 2 or more foci = 2+. The number of liver IL-1 and IL-2 positive cells was measured by systematically scoring at least 100 hepatocyte cells per field in 10 fields of tissue sections by a magnification of 100. Results Xanthine oxidase (XO) activity and lipid peroxidation was significantly different in the allopurinol group compared to the saline group (XO; 0.098 ± 0.006 mU/mg vs. 0.162 ± 0.008 mU/mg, p = 0.01, 0.116 ± 0.040 nmol malondialdehyde/mg versus 0.246 ± 0.040 nmol malondialdehyde /mg, p = 0.01). The allopurinol group had lower histopathological scores, IL-1 and IL-2 immunoexpression levels in the liver compared to the saline group (2.13 ± 0.35 against 5.45 ± 0.24, p = 0.003, IL-1; 5.76 ± 0.43 against 12.85 ± 3.26, p = 0.023, IL-2; 8.55 ± 1.14 against 56.23 ± 7.12, p = 0.002). Conclusions Allopurinol has a therapeutic role against the progression of NAFLD of the rats.
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Affiliation(s)
- V. Barişik
- Metropol Medicine Center - Department of Internal Medicine
| | - H.A. Korkmaz
- “Dr. Behcet Uz” Children’s Hospital - Division of Pediatric Endocrinology
| | - Y.E. Çekdemir
- “Dokuz Eylül” University - Department of Radiology Izmir
| | - D. Torlak
- Acibadem University - Department of Pediatrics, Istanbul
| | - H. Aktuğ
- Ege University - Department of Histology and Embryology
| | - A. Yavaşoğlu
- Ege University - Department of Histology and Embryology
| | - O. Erbaş
- Ege University - Department of Physiology, Izmir, Turkey
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Martins TDO, Ramos RC, Possidonio G, Bosculo MRM, Oliveira PL, Costa LR, Zamboni VAG, Marques MG, de Almeida BFM. Feline obesity causes hematological and biochemical changes and oxidative stress - a pilot study. Vet Res Commun 2023; 47:167-177. [PMID: 35778642 DOI: 10.1007/s11259-022-09940-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 05/17/2022] [Indexed: 01/27/2023]
Abstract
Obesity, an extremely important factor in feline clinical practice, is estimated to affect up to one third of the feline population. Moreover, it can trigger chronic inflammation, which could predispose to oxidative stress by increasing reactive oxygen species, thereby generating potentially irreversible cellular damage. This study analyzed hematological, biochemical and oxidative stress profiles at various degrees of feline obesity. Forty-five cats were selected and divided into three groups: control (n = 17), overweight (n = 13) and obese (n = 15), after clinical and laboratory evaluation and body condition score. Biochemical and oxidative stress analyses were performed using a photocolorimeter and hematological analyses were performed in a veterinary cell counter. Obese cats showed increased mean corpuscular volume (MCV), red cell distribution width (RDW), HDL cholesterol and triglycerides and decreased activity of gamma-glutamyl transferase (GGT) than control cats, although within the reference ranges for the species. As for oxidative stress, obese cats showed higher total antioxidant capacity (TAC), by the inhibition of 2,2'-Azino-Bis-3-Ethylbenzthiazoline-6-Sulfonic Acid (ABTS), inhibition of ABTS associated with horseradish peroxidase (ABTS + HRP), cupric ion reducing antioxidant capacity (CUPRAC) and ferric reducing antioxidant power (FRAP) methods, while overweight cats had a higher TAC-ABTS + HRP and TAC-FRAP than control cats. We conclude that the conditions of natural obesity and overweight in the feline species alter its hematological, biochemical and oxidative stress parameters.
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Affiliation(s)
- Tainara de Oliveira Martins
- Roque Quagliato Veterinary Hospital, University Center of the Integrated Faculties of Ourinhos (Unifio), Rodovia BR 153, km 338, Bairro Água do Cateto, 19909-100, Ourinhos, SP, Brazil
| | - Rebecca Cápera Ramos
- Roque Quagliato Veterinary Hospital, University Center of the Integrated Faculties of Ourinhos (Unifio), Rodovia BR 153, km 338, Bairro Água do Cateto, 19909-100, Ourinhos, SP, Brazil
| | - Geovana Possidonio
- Roque Quagliato Veterinary Hospital, University Center of the Integrated Faculties of Ourinhos (Unifio), Rodovia BR 153, km 338, Bairro Água do Cateto, 19909-100, Ourinhos, SP, Brazil
| | - Maria Rachel Melo Bosculo
- Roque Quagliato Veterinary Hospital, University Center of the Integrated Faculties of Ourinhos (Unifio), Rodovia BR 153, km 338, Bairro Água do Cateto, 19909-100, Ourinhos, SP, Brazil
| | - Paula Lima Oliveira
- Faculty of Veterinary Medicine of Araçatuba, São Paulo State University (FMVA-Unesp), Araçatuba, SP, Brazil
| | - Leticia Ramos Costa
- Roque Quagliato Veterinary Hospital, University Center of the Integrated Faculties of Ourinhos (Unifio), Rodovia BR 153, km 338, Bairro Água do Cateto, 19909-100, Ourinhos, SP, Brazil
| | - Vinicius Aquiles Gomes Zamboni
- Roque Quagliato Veterinary Hospital, University Center of the Integrated Faculties of Ourinhos (Unifio), Rodovia BR 153, km 338, Bairro Água do Cateto, 19909-100, Ourinhos, SP, Brazil
| | - Marcel Gambin Marques
- Roque Quagliato Veterinary Hospital, University Center of the Integrated Faculties of Ourinhos (Unifio), Rodovia BR 153, km 338, Bairro Água do Cateto, 19909-100, Ourinhos, SP, Brazil
| | - Breno Fernando Martins de Almeida
- Roque Quagliato Veterinary Hospital, University Center of the Integrated Faculties of Ourinhos (Unifio), Rodovia BR 153, km 338, Bairro Água do Cateto, 19909-100, Ourinhos, SP, Brazil. .,Faculty of Veterinary Medicine of Araçatuba, São Paulo State University (FMVA-Unesp), Araçatuba, SP, Brazil.
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Li S, Liu J, Wang Z, Duan F, Jia Z, Chen X, Li S. The promising role of probiotics/prebiotics/synbiotics in energy metabolism biomarkers in patients with NAFLD: A systematic review and meta-analysis. Front Public Health 2022; 10:862266. [PMID: 35958869 PMCID: PMC9358257 DOI: 10.3389/fpubh.2022.862266] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 07/01/2022] [Indexed: 11/13/2022] Open
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a high prevalence worldwide, seriously harming human health, and its pathogenesis remains unclear. In recent years, increasing evidence has indicated that intestinal microbiota plays an important role in the occurrence and development of NAFLD. The regulation method of probiotics/prebiotics/synbiotics can alter the intestinal microbiota and has been suggested as an option in the treatment of NAFLD. Methods Five databases of PubMed, Embase, the Cochrane Library, clinicaltrails.gov, and China National Knowledge Infrastructure were searched initially, and then the eligible studies were screened. Finally, the data of included studieswere extracted, combined and analyzed Results A total of 29 randomized controlled trials involving 2,110 patients were included in this study. The results showed that using probiotics/prebiotics/synbiotics in the intervention group could reduce the levels of glucose (SMD = −0.23, 95% CI [−0.45, −0.01], P = 0.04), HOMA-IR (SMD = −0.47, 95% CI [−0.63, −0.31], P < 0.00001) and insulin (SMD = −0.46, 95% CI [−0.76, −0.16], P = 0.002) in sugar metabolism; in terms of lipid metabolism, the levels of TC (SMD = −0.62, 95%CI [−0.87, −0.36], P < 0.00001), and LDL-C (SMD = −0.57, 95%CI [−0.85, −0.28], P < 0.00001) were decreased; and the level of ALB was decreased in protein metabolism (SMD = −0.34, 95%CI [−0.61, −0.06], P = 0.02). Conclusions Based on the current evidence, probiotics/prebiotics/synbiotics may improve energy metabolism biomarkers in the NAFLD population, but these effects still need to be confirmed by further research. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/#aboutpage.
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Affiliation(s)
- Shudi Li
- Henan University of Chinese Medicine, Zhengzhou, China
| | - Jiangkai Liu
- The First Affiliated Hospital of Henan University of TCM, Zhengzhou, China
| | - Zhen Wang
- The First Affiliated Hospital of Henan University of TCM, Zhengzhou, China
| | - Fei Duan
- The First Affiliated Hospital of Henan University of TCM, Zhengzhou, China
| | - Zi Jia
- Henan University of Chinese Medicine, Zhengzhou, China
| | - Xinju Chen
- The First Affiliated Hospital of Henan University of TCM, Zhengzhou, China
| | - Suling Li
- The First Affiliated Hospital of Henan University of TCM, Zhengzhou, China
- *Correspondence: Suling Li
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9
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Chaves AB, Miranda ER, Mey JT, Blackburn BK, Fuller KNZ, Stearns B, Ludlow A, Williamson DL, Houmard JA, Haus JM. Exercise reduces the protein abundance of TXNIP and its interacting partner REDD1 in skeletal muscle: potential role for a PKA-mediated mechanism. J Appl Physiol (1985) 2022; 132:357-366. [PMID: 34941434 PMCID: PMC8791844 DOI: 10.1152/japplphysiol.00229.2021] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Thioredoxin-interacting protein (TXNIP) negatively effects the redox state and growth signaling via its interactions with thioredoxin (TRX) and regulated in development and DNA damage response 1 (REDD1), respectively. TXNIP expression is downregulated by pathways activated during aerobic exercise (AE), via posttranslational modifications (PTMs; serine phosphorylation and ubiquitination). The purpose of this investigation was to determine the effects of acute AE on TXNIP expression, posttranslational modifications, and its interacting partners, REDD1 and TRX. Fifteen healthy adults performed 30 min of aerobic exercise (80% V̇o2max) with muscle biopsies taken before, immediately following, and 3 h following the exercise bout. To explore potential mechanisms underlying our in vivo findings, primary human myotubes were exposed to two models of exercise, electrical pulse stimulation (EPS) and palmitate-forskolin-ionomycin (PFI). Immediately following exercise, TXNIP protein decreased, but returned to preexercise levels 3 h after exercise. These results were replicated in our PFI exercise model only. Although not statistically significant, there was a trending main effect in serine-phosphorylation status of TXNIP (P = 0.07) immediately following exercise. REDD1 protein decreased 3 h after exercise. AE had no effect on TRX protein expression, gene expression, or the activity of its reducing enzyme, thioredoxin reductase. Consequently, AE had no effect on the TRX: TXNIP interaction. Our results indicate that AE leads to acute reductions in TXNIP and REDD1 protein expression. However, these changes did not result in alterations in the TRX: TXNIP interaction and could not be entirely explained by alterations in TXNIP PTMs or changes in TRX expression or activity.NEW & NOTEWORTHY Aerobic exercise is an effective tool in the prevention and treatment of several chronic metabolic diseases. However, the mechanisms through which these benefits are conferred have yet to be fully elucidated. Our data reveal a novel effect of aerobic exercise on reducing the protein expression of molecular targets that negatively impact redox and insulin/growth signaling in skeletal muscle. These findings contribute to the expanding repository of molecular signatures provoked by aerobic exercise.
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Affiliation(s)
- Alec B. Chaves
- 1Human Performance Laboratory, Department of Kinesiology, East Carolina University, Greenville, North Carolina
| | - Edwin R. Miranda
- 2School of Kinesiology, University of Michigan, Ann Arbor, Michigan
| | - Jacob T. Mey
- 3Integrated Physiology and Molecular Metabolism, Pennington Biomedical Research Center, Baton Rouge, Louisiana
| | - Brian K. Blackburn
- 4Applied Health Sciences and Kinesiology, Humboldt State University, Arcata, California
| | - Kelly N. Z. Fuller
- 5Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas
| | - Blaise Stearns
- 2School of Kinesiology, University of Michigan, Ann Arbor, Michigan
| | - Andrew Ludlow
- 2School of Kinesiology, University of Michigan, Ann Arbor, Michigan
| | - David L. Williamson
- 6School of Behavioral Sciences and Education, Penn State University Harrisburg, Middletown, Pennsylvania
| | - Joseph A. Houmard
- 1Human Performance Laboratory, Department of Kinesiology, East Carolina University, Greenville, North Carolina
| | - Jacob M. Haus
- 2School of Kinesiology, University of Michigan, Ann Arbor, Michigan
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10
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Motamed B, Kohansal Vajargah M, Kalantari S, Shafaghi A. HOMA-IR index in non-diabetic patient, a reliable method for early diagnosis of liver steatosis. CASPIAN JOURNAL OF INTERNAL MEDICINE 2022; 13:519-526. [PMID: 35974947 PMCID: PMC9348208 DOI: 10.22088/cjim.13.3.519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 02/01/2021] [Accepted: 03/17/2021] [Indexed: 11/22/2022]
Abstract
Background NAFLD is one of the most common liver diseases in the world. HOMA-IR as an indicator of insulin resistance is commonly used in clinical trials in NAFLD patients. The aim of this study was to evaluate the application of HOMA-IR index in the diagnosis of NAFLD. Methods This study was performed on 54 patients with NAFLD and 54 non-NAFLD patients that referred to Razi Hospital in Rasht during 2019-2020. FibroScan was used to diagnose NAFLD in the patient group and ultrasound was used to rule it out in the control group. Metabolic and hepatic parameters were measured for each patient. Data were entered into SPSS 22 software and the necessary analyses were performed. Results The mean age of the subjects in the study was 44.01±13.12 years and ranged from 18 to 75 years. 72.2% of people affected by NAFLD were men (p <0.001) .The optimal cut-off point for HOMA-IR in NAFLD was 1.65 with a sensitivity of 89.7% and a specificity of 76.9% in men and 1.90 with a sensitivity of 86.7% and a specificity of 82.9% in women. Overall, the optimal cut-off point for HOMA-IR in NAFLD was 1.75 with a sensitivity of 87.0% and a specificity of 81.5%. In addition, the results showed that there was no significant relationship between steatosis and hepatic fibrosis with HOMA-IR index. Conclusion The results showed that HOMA-IR can be used as a reliable criterion for early detection of NAFLD.
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Affiliation(s)
- Behrang Motamed
- Department of Internal Medicine, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Mahsa Kohansal Vajargah
- Department of Internal Medicine, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Saeed Kalantari
- Razi Clinical Research Development Unit, Guilan University of Medical Sciences, Rasht, Iran
| | - Afshin Shafaghi
- GI Cancer Screening and Prevention Research Center, Guilan University of Medical Sciences, Rasht, Iran
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11
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Arya A, Azarmehr N, Mansourian M, Doustimotlagh AH. Inactivation of the superoxide dismutase by malondialdehyde in the nonalcoholic fatty liver disease: a combined molecular docking approach to clinical studies. Arch Physiol Biochem 2021; 127:557-564. [PMID: 31475569 DOI: 10.1080/13813455.2019.1659827] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The objective of the present study was to investigate the plasma levels of oxidative stress markers and the activity of antioxidant enzymes in NAFLD and healthy subjects. Furthermore, the interaction behaviors of malondialdehyde (MDA) with Cu/Zn superoxide dismutase (SOD1) enzyme were elucidated by molecular docking. The study involved 60 patients with NAFLD and 25 healthy volunteers. The plasma levels of oxidative stress parameters and antioxidant enzymes activity were determined. NAFLD patients had significantly higher alanine aminotransferase, MDA and nitric oxide metabolites values, as well as significantly lower total thiol and SOD activity than the control group. Based on the molecular docking, MDA could deactivate the enzymatic activity of SOD1. Impaired antioxidant defense systems may be involved in the progression of NAFLD. This study provides direct evidence at a molecular level to explain that MDA may exert its oxidant activity by specific action within the specific molecular pathway.HighlightsImpairing antioxidant defense systems may be a main factor in the progression of nonalcoholic fatty liver disease (NAFLD).Increasing MDA and NO metabolites, as well as decreasing TSH values and SOD activity in NAFLD patients as compared to control subjectsIncreasing MDA level in NAFLD patients may be inactivate SOD activity by reaction with the key residues Cu ion inside active site of the enzyme catalytic site.
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Affiliation(s)
- Arash Arya
- Internal Medicine, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Nahid Azarmehr
- Student Research Committee, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Mahboubeh Mansourian
- Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Amir Hossein Doustimotlagh
- Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
- Department of Clinical Biochemistry, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran
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12
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Total Sesquiterpene Glycosides from Loquat Leaves Ameliorate HFD-Induced Insulin Resistance by Modulating IRS-1/GLUT4, TRPV1, and SIRT6/Nrf2 Signaling Pathways. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:4706410. [PMID: 34745416 PMCID: PMC8566052 DOI: 10.1155/2021/4706410] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 09/19/2021] [Accepted: 10/05/2021] [Indexed: 12/12/2022]
Abstract
Loquat (Eriobotrya japonica Lindl.), a subtropical fruit tree native to Asia, is not only known to be nutritive but also beneficial for the treatment of diabetes in the south of China. To expand its development, this study was undertaken concerning the potential therapeutic role of total sesquiterpene glycosides (TSGs) from loquat leaves in insulin resistance (IR), the major causative factor of type 2 diabetes mellitus (T2DM). Male C57BL/6 mice were fed on high-fat diet (HFD) to induce IR and then were given TSG by oral administration at 25 and 100 mg/kg/day, respectively. TSG notably improved metabolic parameters including body weight, serum glucose, and insulin levels and prevented hepatic injury. Moreover, inflammatory response and oxidative stress were found to be remarkably alleviated in IR mice with TSG supplement. Further research in liver of IR mice demonstrated that TSG repaired the signalings of insulin receptor substrate-1 (IRS-1)/glucose transporter member 4 (GLUT4) and AMP-activated protein kinase (AMPK), which improved glucose and lipid metabolism and prevented lipid accumulation in liver. It was also observed that TSG suppressed the expression of transient receptor potential vanilloid 1 (TRPV1), whereas the signaling pathway of sirtuin-6 (SIRT6)/nuclear factor erythroid 2-related factor 2 (Nrf2) was significantly promoted. Based on the results, the current study demonstrated that TSG from loquat leaves potentially ameliorated IR in vivo by enhancing IRS-1/GLUT4 signaling and AMPK activation and modulating TRPV1 and SIRT6/Nrf2 signaling pathways.
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13
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Basarir G, Ozcabi B, Aksu Sayman O, Ozturkmen Akay H, Yildiz FM. Evaluation of clinical, endocrine and metabolic findings in obese children with and without hepatosteatosis. J Pediatr Endocrinol Metab 2021; 34:1081-1087. [PMID: 34142516 DOI: 10.1515/jpem-2021-0034] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 05/12/2021] [Indexed: 12/30/2022]
Abstract
OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is a common obesity-related comorbidity in childhood. In this study, we aimed to evaluate predictors of NAFLD by comparing clinical, endocrine and metabolic findings in obese children with and without hepatosteatosis. METHODS Two hundred and eight obese children aged 6-18 years were included. The patients were divided into group 1 (patients with NAFLD, n=94) and group 2 (patients without NAFLD, n=114). Anthropometric measurements, pubertal stage, lipid profiles, fasting glucose and insulin, homeostatic model of assessment for insulin resistance (HOMA-IR), uric acid, total bilirubin, alanine aminotransferase (ALT), blood urea nitrogen, thyroid-stimulating hormone and free thyroxine parameters were compared retrospectively. RESULTS The mean body weight, body mass index (BMI), height, tri-ponderal mass index (TMI), insulin, HOMA-IR, triglyceride, ALT and uric acid values were significantly higher, while high-density lipoprotein-cholesterol (HDL-C) values were significantly lower in group 1. The 70.7% of obese children with hepatosteatosis and 83.9% of those without hepatosteatosis were correctly estimated by parameters including age, gender, ALT, HDL-C, fasting insulin and uric acid values. CONCLUSIONS Since obesity-associated hepatosteatosis induces various long-term metabolic impacts in children, early detection is of critical importance. Age, gender, TMI, BMI, ALT, HDL-C, fasting insulin and uric acid values may help to predict the risk of hepatosteatosis. Besides, we assessed whether TMI compared to BMI does not have a better utility in estimating obesity-induced hepatosteatosis in children. This is the first study to show the association between TMI and hepatosteatosis in children.
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Affiliation(s)
- Gunce Basarir
- Department of Pediatric Neurology, University of Health Sciences, Tepecik Training and Research Hospital, Konak, Izmir, Turkey
| | - Bahar Ozcabi
- Department of Pediatrics, Division of Pediatric Endocrinology, Zeynep Kamil Women and Children's Diseases Training and Research Hospital, Üsküdar, Istanbul, Turkey
| | - Ozden Aksu Sayman
- Department of Pediatrics, University of Health Sciences, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey
| | | | - Feyza M Yildiz
- Department of Pediatrics, Zeynep Kamil Women and Children's Diseases Training and Research Hospital, Üsküdar, Istanbul, Turkey
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14
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Kanoni S, Kumar S, Amerikanou C, Kurth MJ, Stathopoulou MG, Bourgeois S, Masson C, Kannt A, Cesarini L, Kontoe MS, Milanović M, Roig FJ, Beribaka M, Campolo J, Jiménez-Hernández N, Milošević N, Llorens C, Smyrnioudis I, Francino MP, Milić N, Kaliora AC, Trivella MG, Ruddock MW, Medić-Stojanoska M, Gastaldelli A, Lamont J, Deloukas P, Dedoussis GV, Visvikis-Siest S. Nutrigenetic Interactions Might Modulate the Antioxidant and Anti-Inflammatory Status in Mastiha-Supplemented Patients With NAFLD. Front Immunol 2021; 12:683028. [PMID: 34025683 PMCID: PMC8138178 DOI: 10.3389/fimmu.2021.683028] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 04/23/2021] [Indexed: 12/15/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with no therapeutic consensus. Oxidation and inflammation are hallmarks in the progression of this complex disease, which also involves interactions between the genetic background and the environment. Mastiha is a natural nutritional supplement known to possess antioxidant and anti-inflammatory properties. This study investigated how a 6-month Mastiha supplementation (2.1 g/day) could impact the antioxidant and inflammatory status of patients with NAFLD, and whether genetic variants significantly mediate these effects. We recruited 98 patients with obesity (BMI ≥ 30 kg/m2) and NAFLD and randomly allocated them to either the Mastiha or the placebo group for 6 months. The anti-oxidative and inflammatory status was assessed at baseline and post-treatment. Genome-wide genetic data was also obtained from all participants, to investigate gene-by-Mastiha interactions. NAFLD patients with severe obesity (BMI > 35kg/m2) taking the Mastiha had significantly higher total antioxidant status (TAS) compared to the corresponding placebo group (P value=0.008). We did not observe any other significant change in the investigated biomarkers as a result of Mastiha supplementation alone. We identified several novel gene-by-Mastiha interaction associations with levels of cytokines and antioxidant biomarkers. Some of the identified genetic loci are implicated in the pathological pathways of NAFLD, including the lanosterol synthase gene (LSS) associated with glutathione peroxidase activity (Gpx) levels, the mitochondrial pyruvate carrier-1 gene (MPC1) and the sphingolipid transporter-1 gene (SPNS1) associated with hemoglobin levels, the transforming growth factor‐beta‐induced gene (TGFBI) and the micro-RNA 129-1 (MIR129-1) associated with IL-6 and the granzyme B gene (GZMB) associated with IL-10 levels. Within the MAST4HEALTH randomized clinical trial (NCT03135873, www.clinicaltrials.gov) Mastiha supplementation improved the TAS levels among NAFLD patients with severe obesity. We identified several novel genome-wide significant nutrigenetic interactions, influencing the antioxidant and inflammatory status in NAFLD.
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Affiliation(s)
- Stavroula Kanoni
- William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Satish Kumar
- EA_1122, IGE-PCV, Université de Loraine, Nancy, France
| | - Charalampia Amerikanou
- Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece
| | - Mary Jo Kurth
- Randox Laboratories Ltd (RANDOX), Crumlin, United Kingdom
| | | | - Stephane Bourgeois
- William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | | | - Aimo Kannt
- Fraunhofer Institute of Translational Medicine and Pharmacology, Frankfurt, Germany
| | - Lucia Cesarini
- ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | | | - Maja Milanović
- Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
| | - Francisco J Roig
- Biotechvana, Parc Científic, Universitat de València, Valencia, Spain.,Facultad de Ciencias de la Salud, Universidad San Jorge, Zaragoza, Spain
| | - Mirjana Beribaka
- Department of Biology, Faculty of Technology Zvornik, University of East Sarajevo, Zvornik, Bosnia and Herzegovina
| | - Jonica Campolo
- ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.,Institute of Clinical Physiology National Research Council, Pisa, Italy
| | - Nuria Jiménez-Hernández
- Area de Genòmica i Salut, Fundació per al Foment de la Investigació Sanitária i Biomèdica de la Comunitat Valenciana (FISABIO-Salut Pública), Valencia, Spain.,CIBER en Epidemiología y Salud Pública, Madrid, Spain
| | | | - Carlos Llorens
- Biotechvana, Parc Científic, Universitat de València, Valencia, Spain
| | | | - M Pilar Francino
- Area de Genòmica i Salut, Fundació per al Foment de la Investigació Sanitária i Biomèdica de la Comunitat Valenciana (FISABIO-Salut Pública), Valencia, Spain.,CIBER en Epidemiología y Salud Pública, Madrid, Spain
| | - Nataša Milić
- Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
| | - Andriana C Kaliora
- Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece
| | - Maria Giovanna Trivella
- ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.,Institute of Clinical Physiology National Research Council, Pisa, Italy
| | - Mark W Ruddock
- Randox Laboratories Ltd (RANDOX), Crumlin, United Kingdom
| | - Milica Medić-Stojanoska
- Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.,Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Vojvodina, Novi Sad, Serbia
| | | | - John Lamont
- Randox Laboratories Ltd (RANDOX), Crumlin, United Kingdom
| | - Panos Deloukas
- William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.,Centre for Genomic Health, Life Sciences, Queen Mary University of London, London, United Kingdom
| | - George V Dedoussis
- Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece
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15
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Ghassemi M, Hosseinchi S, Seirafianpour F, Dodangeh M, Goodarzi A. Non-alcoholic fatty liver and lipid profile status in patients with melasma: A case-control study. J Cosmet Dermatol 2021; 20:3656-3660. [PMID: 33609335 DOI: 10.1111/jocd.14014] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 01/13/2021] [Accepted: 02/16/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND There are pieces of evidence regarding the association between melasma and metabolic syndrome. To assess the prevalence and grade of nonalcoholic fatty liver and lipid profile status in patients with melasma, we designed this case-control study. METHODS This study was performed on 30 consecutive women with melasma who referred to the dermatology clinic of the hospital as the case group and 34 healthy women. For all participants, serum lipid profiles and liver enzymes were checked. Also, the existence of fatty liver was assessed by ultrasonography. RESULTS Except for serum level of LDL (low-density lipoprotein) that was significantly higher in the melasma group than in the healthy group (104.23 ± 25.00 mg/dl versus 89.85 ± 23.00 mg/dl, p = 0.020), the level of other parameters including other lipid profiles, blood sugar, or liver enzymes was similar in both groups. In ultrasonography, the overall prevalence of fatty liver was 23.3% in the melasma group and 20.6% in the control group, and no difference was found between the two groups in grade of fatty liver (p = 0.791). CONCLUSION The study showed a higher serum LDL level in patients with melasma compared to women without melasma, but there was no difference between the groups in prevalence or grade of fatty liver.
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Affiliation(s)
- Mohammadreza Ghassemi
- Dermatology Department, Rasool Akram Medical Complex, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | | | - Farnoosh Seirafianpour
- Student Research Committee, School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Milad Dodangeh
- Student Research Committee, School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Azadeh Goodarzi
- Dermatology Department, Rasool Akram Medical Complex, Iran University of Medical Sciences (IUMS), Tehran, Iran
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16
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Baratta F, Pastori D, Bartimoccia S, Cammisotto V, Cocomello N, Colantoni A, Nocella C, Carnevale R, Ferro D, Angelico F, Violi F, Del Ben M. Poor Adherence to Mediterranean Diet and Serum Lipopolysaccharide are Associated with Oxidative Stress in Patients with Non-Alcoholic Fatty Liver Disease. Nutrients 2020; 12:1732. [PMID: 32531941 PMCID: PMC7352324 DOI: 10.3390/nu12061732] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 06/05/2020] [Accepted: 06/07/2020] [Indexed: 12/17/2022] Open
Abstract
Oxidative stress plays a pivotal role in non-alcoholic fatty liver disease (NAFLD). Factors inducing oxidative stress in NAFLD may be several; however, a relationship with the adherence to Mediterranean Diet (Med-diet) and with serum lipopolysaccharide (LPS) has been poorly investigated in this setting. The aim was to investigate factors associated with impaired oxidative stress in NAFLD, focusing on the potential role of LPS and Med-diet. We enrolled 238 consecutive outpatients from the PLINIO study, in whom we measured the soluble Nox2-derived peptide (sNox2-dp), a marker of systemic oxidative stress, and serum LPS. Adherence to Med-diet was investigated by a nine-item validated dietary questionnaire. Serum sNox2-dp and LPS were higher in patients with NAFLD compared to those without (25.0 vs. 9.0 pg/mL, p < 0.001 and 62.0 vs. 44.9 pg/mL, p < 0.001, respectively). In patients with NAFLD, the highest sNox2-dp tertile was associated with the top serum LPS tertile (Odds Ratio (OR): 4.71; p < 0.001), APRI > 0.7 (OR: 6.96; p = 0.005) and Med-diet-score > 6 (OR: 0.14; p = 0.026). Analyzing individual foods, the daily consumption of wine (OR: 0.29, p = 0.046) and the adequate weekly consumption of fish (OR: 0.32, p = 0.030) inversely correlated with the top sNox2-dp tertile. In conclusion, patients with NAFLD showed impaired oxidative stress. Levels of sNox2 correlated with serum LPS and with low adherence to Med-Diet.
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Affiliation(s)
- Francesco Baratta
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
| | - Daniele Pastori
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
| | - Simona Bartimoccia
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
| | - Vittoria Cammisotto
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
| | - Nicholas Cocomello
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
| | - Alessandra Colantoni
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
| | - Cristina Nocella
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
| | - Roberto Carnevale
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04015 Latina, Italy;
- Mediterranea Cardio Centro, 80122 Napoli, Italy
| | - Domenico Ferro
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
| | - Francesco Angelico
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Roma, Italy
| | - Francesco Violi
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
- Mediterranea Cardio Centro, 80122 Napoli, Italy
| | - Maria Del Ben
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
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Ke Z, Zhao Y, Tan S, Chen H, Li Y, Zhou Z, Huang C. Citrus reticulata Blanco peel extract ameliorates hepatic steatosis, oxidative stress and inflammation in HF and MCD diet-induced NASH C57BL/6 J mice. J Nutr Biochem 2020; 83:108426. [PMID: 32559586 DOI: 10.1016/j.jnutbio.2020.108426] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 04/04/2020] [Accepted: 05/03/2020] [Indexed: 12/31/2022]
Abstract
Excessive lipid deposition, oxidative stress and inflammation in liver tissues are regarded as crucial inducers of nonalcoholic steatohepatitis (NASH), which is the most frequent chronic liver disease and closely related to obesity and insulin resistance. In this work, the preventive and therapeutic effects of Citrus reticulata Blanco (Jizigan) peel extract (JZE) on NASH induced by high fat (HF) diet and methionine choline-deficient (MCD) diet in C57BL/6 mice were investigated. We found that daily supplementation of JZE with an HF diet effectively ameliorated glucose tolerance and insulin resistance. In addition, the key indexes of lipid profiles, oxidative stress, hepatic steatosis and inflammatory factors were also ameliorated in both NASH mouse models. Furthermore, JZE treatment activated nuclear factor erythroid-2-related factor 2 (Nrf2) in the livers of diet- induced NASH mice. Our study suggests that JZE might alleviate NASH via the activation of Nrf2 signaling and that citrus Jizigan could be used as a dietary therapy for NASH and related metabolic syndrome.
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Affiliation(s)
- Zunli Ke
- Morphological Laboratory, Basic Medical School, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025, China; Drug Discovery Lab, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; College of Horticulture and Landscape Architecture, Southwest University, Chongqing 400716, China
| | - Yuanyuan Zhao
- Drug Discovery Lab, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Si Tan
- School of Advanced Agriculture and Bioengineering, Yangtze Normal University, Fuling, 408100, Chongqing, China
| | - Hui Chen
- Drug Discovery Lab, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yin Li
- Drug Discovery Lab, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Zhiqin Zhou
- College of Horticulture and Landscape Architecture, Southwest University, Chongqing 400716, China
| | - Cheng Huang
- Drug Discovery Lab, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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18
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Zhang CH, Xiao Q, Sheng JQ, Liu TT, Cao YQ, Xue YN, Shi M, Cao Z, Zhou LF, Luo XQ, Deng KZ, Chen C. Gegen Qinlian Decoction abates nonalcoholic steatohepatitis associated liver injuries via anti-oxidative stress and anti-inflammatory response involved inhibition of toll-like receptor 4 signaling pathways. Biomed Pharmacother 2020; 126:110076. [PMID: 32169759 DOI: 10.1016/j.biopha.2020.110076] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 03/01/2020] [Accepted: 03/03/2020] [Indexed: 02/07/2023] Open
Abstract
Gegen Qilian Decoction (GGQLD) is a well-established classic Chinese medicine prescription in treating nonalcoholic steatohepatitis (NASH). However, the molecular mechanism of GGQLD action on NASH is still not clear. This study aimed to assess the anti-NASH effect of GGQLD, and to explore its molecular mechanisms in vivo and in vitro. In HFD-fed rats, GGQLD decreased significantly serum triglyceride (TG), cholesterol (CHO), total bile acid (TBA), low-density lipoprotein (LDL), free fatty acid (FFA) and lipopolysaccharide (LPS) levels, increased levels of differentially expressed proteins (DEPs) Ahcy, Gpx1, Mat1a, GNMT, and reduced the expression of ALDOB. In RAW264.7 macrophages, GGQLD reduced the expression levels of inflammatory factors TNF-α and IL-6 mRNA, and diminished NASH by increasing differentially expressed genes (DEGs) CBS, Mat1a, Hnf4α and Pparα to reduce oxidative stress or lipid metabolism. The results of DEGs verification also showed that GGQLD up-regulated expressions of Hnf4α, Pparα and Cbs genes. In HepG2 cells, GGQLD decreased IL-6 levels and intracellular TG content, and inhibited FFA-induced expression of toll-like receptor 4 (TLR4). In summary, GGQLD abates NASH associated liver injuries via anti-oxidative stress and anti-inflammatory response involved inhibition of TLR4 signal pathways. These findings provide new insights into the anti-NASH therapy by GGQLD.
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Affiliation(s)
- Chang-Hua Zhang
- College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Qin Xiao
- College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Jun-Qing Sheng
- College of Life Science, Nanchang University, Nanchang, 330031, PR China.
| | - Tong-Tong Liu
- College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Ying-Qian Cao
- College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Ya-Nan Xue
- College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Min Shi
- College of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Zheng Cao
- College of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Li-Fen Zhou
- Large Precise Instruments Shared Services Center of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Xiao-Quan Luo
- Experimental Animal Science and Technology Center of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, PR China
| | - Ke-Zhong Deng
- College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Chen Chen
- School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia.
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Dietary Platycodon grandiflorus Attenuates Hepatic Insulin Resistance and Oxidative Stress in High-Fat-Diet Induced Non-Alcoholic Fatty Liver Disease. Nutrients 2020; 12:nu12020480. [PMID: 32074961 PMCID: PMC7071327 DOI: 10.3390/nu12020480] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Revised: 01/26/2020] [Accepted: 02/11/2020] [Indexed: 12/18/2022] Open
Abstract
The root of Platycodon grandiflorus (PG), with hepatoprotective and anti-oxidation effects, has a long history of being used as food and herbal medicine in Asia. However, the mechanism of PG against non-alcoholic fatty liver disease (NAFLD) is still not clear. The aim of this study was to investigate the mechanism of PG suppressing the development of NAFLD induced by a high-fat diet (HFD) in mice. Male C57BL/6J mice were fed with either a standard chow diet or a HFD, either supplemented with or without PG, for 16 weeks. Serum lipids, liver steatosis, oxidative stress and insulin sensitivity were determined. Expressions or activities of hepatic enzymes in the related pathways were analyzed to investigate the mechanisms. PG significantly reduced HFD-induced hepatic injury and hyperlipidemia, as well as hepatic steatosis via regulating phosphorylation of acetyl-CoA carboxylase (p-ACC) and expression of fatty acid synthase (FAS). In addition, PG ameliorated oxidative stress by restoring glutathione (GSH) content and antioxidant activities, and improved insulin sensitivity by regulating the PI3K/Akt/GSK3β signaling pathway. Our data showed that dietary PG have profound effects on hepatic insulin sensitivity and oxidative stress, two key factors in the pathogenesis of NAFLD, demonstrating the potential of PG as a therapeutic strategy for NAFLD.
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20
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Fadaei R, Meshkani R, Poustchi H, Fallah S, Moradi N, Panahi G, Merat S, Golmohammadi T. Association of carotid intima media thickness with atherogenic index of plasma, apo B/apo A-I ratio and paraoxonase activity in patients with non-alcoholic fatty liver disease. Arch Physiol Biochem 2019; 125:19-24. [PMID: 29359590 DOI: 10.1080/13813455.2018.1429475] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND NAFLD patients have higher risk of atherosclerosis cardiovascular disease (ASCVD). apo B/apoA-I ratio and atherogenic index of plasma (AIP) have been suggested as biomarker for ASCVD. METHODS apo A-I, apoB, aryl esterase (ARE) and paraoxonase (PON) activities and carotid intima media thickness (cIMT) were determined in 49 NAFLD patients and 33 controls. RESULTS Plasma levels of apo A-I, adiponectin, ARE and PON activities decreased in NAFLD patients, while apo B, AIP and apoB/apo A-I ratio level were higher in NAFLD patients compared to controls. Furthermore, cIMT showed a positive association with AIP, apo B/apo A-I ratio and AIP + (apo B/apo A-I) in NAFLD patients. Strikingly, AIP + (apo B/apo A-I) showed a good ability to discriminating increased cIMT in NAFLD patients. CONCLUSIONS The result showed that AIP and apo B/apo A-I associated with cIMT in NAFLD patients; however, more study are needed to prove this concept.
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Affiliation(s)
- Reza Fadaei
- a Department of Clinical Biochemistry, Faculty of Medicine , Tehran University of Medical Sciences , Tehran , Iran
| | - Reza Meshkani
- a Department of Clinical Biochemistry, Faculty of Medicine , Tehran University of Medical Sciences , Tehran , Iran
| | - Hossein Poustchi
- b Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute , Tehran University of Medical Sciences , Tehran , Iran
- c Digestive Disease Research Center, Digestive Disease Research Institute , Tehran University of Medical Sciences , Tehran , Iran
| | - Soudabeh Fallah
- d Department of Clinical Biochemistry, Faculty of Medicine , Iran University of Medical Sciences , Tehran , Iran
| | - Nariman Moradi
- e Department of Clinical Biochemistry, Faculty of Medicine , Kurdistan University of Medical Sciences , Sanandaj , Iran
| | - Ghodratollah Panahi
- a Department of Clinical Biochemistry, Faculty of Medicine , Tehran University of Medical Sciences , Tehran , Iran
| | - Shahin Merat
- b Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute , Tehran University of Medical Sciences , Tehran , Iran
- c Digestive Disease Research Center, Digestive Disease Research Institute , Tehran University of Medical Sciences , Tehran , Iran
| | - Taghi Golmohammadi
- a Department of Clinical Biochemistry, Faculty of Medicine , Tehran University of Medical Sciences , Tehran , Iran
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21
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D'Adamo E, Castorani V, Nobili V. The Liver in Children With Metabolic Syndrome. Front Endocrinol (Lausanne) 2019; 10:514. [PMID: 31428049 PMCID: PMC6687849 DOI: 10.3389/fendo.2019.00514] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 07/15/2019] [Indexed: 12/17/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is recognized as an emerging health risk in obese children and adolescents. NAFLD represents a wide spectrum of liver conditions, ranging from asymptomatic steatosis to steatohepatitis. The growing prevalence of fatty liver disease in children is associated with an increased risk of metabolic and cardiovascular complications. NAFLD is considered the hepatic manifestation of Metabolic Syndrome (MetS) and several lines of evidence have reported that children with NAFLD present one or more features of MetS. The pathogenetic mechanisms explaining the interrelationships between fatty liver disease and MetS are not clearly understood. Altough central obesity and insulin resistance seem to represent the core of the pathophysiology in both diseases, genetic susceptibility and enviromental triggers are emerging as crucial components promoting the development of NAFLD and MetS in children. In the present review we have identified and summarizied studies discussing current pathogenetic data of the association between NAFLD and MetS in children.
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Affiliation(s)
- Ebe D'Adamo
- Department of Neonatology, University of Chieti, Chieti, Italy
- *Correspondence: Ebe D'Adamo
| | | | - Valerio Nobili
- Department of Pediatrics, University “La Sapienza”, Rome, Italy
- Hepatology, Gastroenterology and Nutrition Unit, IRCCS “Bambino Gesù” Children's Hospital, Rome, Italy
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22
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Filgueiras MS, Rocha NP, Novaes JF, Bressan J. Vitamin D status, oxidative stress, and inflammation in children and adolescents: A systematic review. Crit Rev Food Sci Nutr 2018; 60:660-669. [PMID: 30596263 DOI: 10.1080/10408398.2018.1546671] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Vitamin D deficiency is considered a global public health problem with high prevalence in children and adolescents. The majority of the studies in the literature have identified a relationship between vitamin D insufficiency/deficiency and obesity, as well as other traditional cardiometabolic risk factors in children and adolescents. Scarce studies address vitamin D status with oxidative stress and inflammation in the young population. The aim of this systematic review was to evaluate the evidence of the association of vitamin D status with oxidative stress and inflammation in children and adolescents. This is a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guideline on reporting systematic reviews. Eight studies were selected for this review. All included studies evaluated inflammatory biomarkers and two out of eight evaluated biomarkers of oxidative stress. The majority of the studies (five out of eight) found association of vitamin D status with biomarkers of oxidative stress and inflammation such as C-reactive protein (CRP), interleukin-6 (IL-6), cathepsin S, vascular cell adhesion molecule-1 (VCAM-1), malondialdehyde (MDA), myeloperoxidase, 3-nitrotyrosine, and superoxide dismutase (SOD). Vitamin D status is associated with oxidative stress and inflammation in the majority of the studies with children and adolescents. Thus, the assessment of vitamin D status is important because it is associated with nontraditional cardiometabolic markers in the pediatric population (review registration: PROSPERO CRD42018109307).
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Affiliation(s)
- M S Filgueiras
- Department of Nutrition and Health, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil
| | - N P Rocha
- Department of Nutrition and Health, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil
| | - J F Novaes
- Department of Nutrition and Health, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil
| | - J Bressan
- Department of Nutrition and Health, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil
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23
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Kim SH, Kwon DY, Kwak JH, Lee S, Lee YH, Yun J, Son TG, Jung YS. Tunicamycin-Induced ER Stress is Accompanied with Oxidative Stress via Abrogation of Sulfur Amino Acids Metabolism in the Liver. Int J Mol Sci 2018; 19:ijms19124114. [PMID: 30567393 PMCID: PMC6321199 DOI: 10.3390/ijms19124114] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Revised: 12/11/2018] [Accepted: 12/17/2018] [Indexed: 12/19/2022] Open
Abstract
Endoplasmic reticulum (ER) stress is involved in non-alcoholic fatty liver disease (NAFLD), but the relationship between oxidative stress, another well-known risk factor of NAFLD, and ER stress has yet to be elucidated. In this study, we treated mice with tunicamycin (TM) (2 mg/kg body weight) for 48 h to induce ER stress in the liver and examined the metabolic pathway that synthesizes the endogenous antioxidant, glutathione (GSH). Tunicamycin (TM) treatment significantly increased mRNA levels of CHOP and GRP78, and induced lipid accumulation in the liver. Lipid peroxidation in the liver tissue also increased from TM treatment (CON vs. TM; 3.0 ± 1.8 vs. 11.1 ± 0.8 nmol MDA/g liver, p < 0.001), which reflects an imbalance between the generation of reactive substances and antioxidant capacity. To examine the involvement of GSH synthetic pathway, we determined the metabolomic changes of sulfur amino acids in the liver. TM significantly decreased hepatic S-adenosylmethionine concentration in the methionine cycle. The levels of cysteine in the liver were increased, while taurine concentration was maintained and GSH levels profoundly decreased (CON vs. TM; 8.7 ± 1.5 vs. 5.4 ± 0.9 µmol GSH/g liver, p < 0.001). These results suggest that abnormal cysteine metabolism by TM treatment resulted in a decrease in GSH, followed by an increase in oxidative stress in the liver. In HepG2 cells, decreased GSH levels were examined by TM treatment in a dose dependent manner. Furthermore, pretreatment with TM in HepG2 cells potentiated oxidative cell death, by exacerbating the effects of tert-butyl hydroperoxide. In conclusion, TM-induced ER stress was accompanied by oxidative stress by reducing the GSH synthesis, which made the liver more susceptible to oxidative stress.
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Affiliation(s)
- Sou Hyun Kim
- College of Pharmacy, Pusan National University, Busan 46241, Korea.
| | - Do-Young Kwon
- Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158-2280, USA.
| | - Jae-Hwan Kwak
- College of Pharmacy, Brain Busan 21 Plus Program, Kyungsung University, Busan 48434, Korea.
| | - Seunghyun Lee
- College of Pharmacy, Pusan National University, Busan 46241, Korea.
| | - Yun-Hee Lee
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea.
| | - Jieun Yun
- Department of Pharmaceutical Engineering, Cheongju University, Cheongju 28503, Korea.
| | - Tae Gen Son
- Division for Research Center, Dongnam Institute of Radiological and Medical Science, Busan 46033, Korea.
| | - Young-Suk Jung
- College of Pharmacy, Pusan National University, Busan 46241, Korea.
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24
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Ke Z, Zhao Z, Zhao Y, Xu X, Li Y, Tan S, Huang C, Zhou Z. PMFs-rich Citrus extract prevents the development of non-alcoholic fatty liver disease in C57BL/6J mice induced by a high-fat diet. J Funct Foods 2018. [DOI: 10.1016/j.jff.2018.05.032] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
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25
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Guifang T, Xiangwen G, Qinhe Y, Yuanyuan L, Guanlong W, Yinji L, Yupei Z, Haizhen Y, Chunmei L, Jinwen Z. Effects of extracts from soothing-liver and invigorating-spleen formulas on the injury induced by oxidative stress in the hepatocytes of rats with non-alcoholic fatty liver disease induced by high-fat diet. J TRADIT CHIN MED 2018. [DOI: 10.1016/s0254-6272(18)30885-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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26
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Guo CH, Chen WL, Liao CH, Huang K, Chen PY, Yang CP. Effects of Chinese Medicinal Formula BNG-1 on Phosphodiesterase 3B Expression, Hepatic Steatosis, and Insulin Resistance in High Fat Diet-induced NAFLD Mice. Int J Med Sci 2018; 15:1194-1202. [PMID: 30123057 PMCID: PMC6097264 DOI: 10.7150/ijms.26941] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Accepted: 06/30/2018] [Indexed: 11/05/2022] Open
Abstract
Background: Chinese medicinal formula BNG-1, a non-specific inhibitor of phospho-diesterases (PDEs), can be considered as a potential anti-inflammatory agent. The present study was aimed at determining the effects of BNG-1 on the development of non-alcoholic fatty liver disease (NAFLD) in mice. Design and Methods: Male CD1 mice were randomly divided into seven groups, the control Con (4) and Con (8)+saline groups were fed a standard control diet for four or eight weeks; the experimental HFD (4) and HFD (8)+saline groups were fed a high fat diet for four or eight weeks; the HFD (8)+LBNG, HFD (8)+MBNG, and HFD (8)+HBNG groups received a high fat diet along with low, moderate or high doses of BNG-1 (0.026, 0.035, and 0.052g/30g body weight) which was administered for the last four weeks of an eight-week experimental period. After the end of experiment, blood and tissue samples were taken and analyzed. Results: Mice in the HFD (4) group had higher levels of alanine aminotransferase (ALT), plasma and hepatic triglyceride and cholesterol, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) compared with mice in the Con (4) group. Mice receiving the high fat diet along with the BNG-1 supplement had decreased body weight gains and lower visceral fat weights compared with the HFD (8)+saline group. They had also significantly reduced levels of abnormal ALT and HOMA-IR, and improved blood lipid profile. BNG-1-treated mice exhibited reduced hepatic lipid accumulation, lower oxidative stress, and decreased expression of pro-inflammatory cytokines (TNF-α and IL-1β). Furthermore, BNG-1 treatment resulted in down-regulation of hepatic cyclic-AMP dependent PDE3B and up-regulation of PDE3B expression in epididymis adipose tissue. Conclusions: BNG-1 mediated changes in PDE3B expression along with reduction in oxidative stress and inflammation. BNG-1 may ameliorate insulin resistance and hepatic steatosis in the NAFLD mouse model.
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Affiliation(s)
- Chih-Hung Guo
- Institute of Biomedical Nutrition, Hung-Kuang University, Taichung 433, Taiwan, ROC.,Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan, ROC
| | - Wen-Long Chen
- Brain Genesis Biotechnology Co., Ltd., Taipei 112, Taiwan, ROC
| | - Chung-Huei Liao
- Brain Genesis Biotechnology Co., Ltd., Taipei 112, Taiwan, ROC
| | - Karin Huang
- Brain Genesis Biotechnology Co., Ltd., Taipei 112, Taiwan, ROC
| | - Pei-Yin Chen
- Department of Recreation and Holistic Wellness, Ming-Dao University, Changhua 523, Taiwan, ROC
| | - Chun-Pai Yang
- Institute of Biomedical Nutrition, Hung-Kuang University, Taichung 433, Taiwan, ROC.,Department of Neurology, Kuang Tien General Hospital, Taichung 433, Taiwan, ROC
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Lavatera critica, a green leafy vegetable, controls high fat diet induced hepatic lipid accumulation and oxidative stress through the regulation of lipogenesis and lipolysis genes. Biomed Pharmacother 2017; 96:1349-1357. [DOI: 10.1016/j.biopha.2017.11.072] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Revised: 11/09/2017] [Accepted: 11/10/2017] [Indexed: 12/11/2022] Open
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28
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Park BH, Yoon JM, Kim JH, Moon JH, Lee YH, Jang SM, Kim YJ. Pathologic Impact of Insulin Resistance and Sensitivity on the Severity of Liver Histopathology in Pediatric Non-Alcoholic Steatohepatitis. Yonsei Med J 2017; 58:756-762. [PMID: 28540988 PMCID: PMC5447106 DOI: 10.3349/ymj.2017.58.4.756] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2016] [Revised: 03/20/2017] [Accepted: 03/21/2017] [Indexed: 12/25/2022] Open
Abstract
PURPOSE Insulin resistance (IR) has an important role in the development of non-alcoholic steatohepatitis (NASH). We aimed to analyze the association between liver histopathology and IR in pediatric patients with NASH. MATERIALS AND METHODS In 24 children with non-alcoholic fatty liver disease (NAFLD), we investigated whether the hepatic pathologic characteristics have relations with following three biochemical indices; IR index including homeostasis model assessment of IR (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and insulin sensitivity indices-free fatty acid (ISI-FFA). RESULTS Among 24 patients, 16 (66.6%) had a high NAFLD activity score (NAS), which is diagnostic of NASH. Higher serum triglyceride level was significantly correlated with a high NAS. Higher steatosis grades were significantly associated with low insulin sensitivity (p=0.023). In addition, severe lobular inflammation was associated with higher IR: HOMA-IR (p=0.014) and QUICKI (p=0.023). Severe fibrosis correlated with low insulin sensitivity and high IR indexes: ISI-FFA (p=0.049), HOMA-IR (p=0.028), and QUICKI (p=0.007). CONCLUSION Patients with high IR had more severe lobular inflammation and hepatic fibrosis. Analyses of biochemical and endocrine parameters can be applied to determine the severity of the hepatic pathologic status in patients with NASH, especially in children who cannot undergo a liver biopsy.
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Affiliation(s)
- Byung Han Park
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Korea
| | - Jung Min Yoon
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Korea
| | - Ja Hye Kim
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Korea
| | - Jin Hwa Moon
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Korea
| | - Young Ho Lee
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Korea
| | - Se Min Jang
- Department of Pathology, Konyang University College of Medicine, Daejeon, Korea
| | - Yong Joo Kim
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Korea.
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Spahis S, Delvin E, Borys JM, Levy E. Oxidative Stress as a Critical Factor in Nonalcoholic Fatty Liver Disease Pathogenesis. Antioxid Redox Signal 2017; 26:519-541. [PMID: 27452109 DOI: 10.1089/ars.2016.6776] [Citation(s) in RCA: 286] [Impact Index Per Article: 35.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
SIGNIFICANCE Nonalcoholic fatty liver disease (NAFLD), characterized by liver triacylglycerol build-up, has been growing in the global world in concert with the raised prevalence of cardiometabolic disorders, including obesity, diabetes, and hyperlipemia. Redox imbalance has been suggested to be highly relevant to NAFLD pathogenesis. Recent Advances: As a major health problem, NAFLD progresses to the more severe nonalcoholic steatohepatitis (NASH) condition and predisposes susceptible individuals to liver and cardiovascular disease. Although NAFLD represents the predominant cause of chronic liver disorders, the mechanisms of its development and progression remain incompletely understood, even if various scientific groups ascribed them to the occurrence of insulin resistance, dyslipidemia, inflammation, and apoptosis. Nevertheless, oxidative stress (OxS) more and more appears as the most important pathological event during NAFLD development and the hallmark between simple steatosis and NASH manifestation. CRITICAL ISSUES The purpose of this article is to summarize recent developments in the understanding of NAFLD, essentially focusing on OxS as a major pathogenetic mechanism. Various attempts to translate reactive oxygen species (ROS) scavenging by antioxidants into experimental and clinical studies have yielded mostly encouraging results. FUTURE DIRECTIONS Although augmented concentrations of ROS and faulty antioxidant defense have been associated to NAFLD and related complications, mechanisms of action and proofs of principle should be highlighted to support the causative role of OxS and to translate its concept into the clinic. Antioxid. Redox Signal. 26, 519-541.
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Affiliation(s)
- Schohraya Spahis
- 1 GI-Nutrition Unit, Research Centre, CHU Ste-Justine, Université de Montréal , Montreal, Quebec, Canada .,2 Department of Nutrition, Université de Montréal , Montreal, Quebec, Canada
| | - Edgard Delvin
- 1 GI-Nutrition Unit, Research Centre, CHU Ste-Justine, Université de Montréal , Montreal, Quebec, Canada .,3 Department of Biochemistry, Université de Montréal , Montreal, Quebec, Canada
| | | | - Emile Levy
- 1 GI-Nutrition Unit, Research Centre, CHU Ste-Justine, Université de Montréal , Montreal, Quebec, Canada .,2 Department of Nutrition, Université de Montréal , Montreal, Quebec, Canada .,4 EPODE International Network , Paris, France
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Kilic E, Özer ÖF, Erek Toprak A, Erman H, Torun E, Kesgin Ayhan S, Caglar HG, Selek S, Kocyigit A. Oxidative Stress Status in Childhood Obesity: A Potential Risk Predictor. Med Sci Monit 2016; 22:3673-3679. [PMID: 27733746 PMCID: PMC5066503 DOI: 10.12659/msm.897965] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Background Childhood obesity characterized by excessive fat in the body is one of the most serious health problems worldwide due to the social, medical, and physiological complications. Obesity and associated diseases are triggering factors for oxidative stress and inflammation. The aim of this study was to explore the possible association between childhood obesity and inflammatory and oxidative status. Material/Methods Thirty-seven obese children and 37 healthy controls selected from among children admitted to BLIND University Paediatrics Department were included in the study. Anthropometric measurements were performed using standard methods. Glucose, lipid parameters, CRP, insulin, total oxidant status (TOS), total anti-oxidant status (TAS) levels, and total thiol levels (TTL) were measured in serum. HOMA index (HOMA-IR) were calculated. The differences between the groups were evaluated statistically using the Mann-Whitney U test. Results Body mass index was significantly higher in the obese group (median: 28.31(p<0.001). Glucose metabolism, insulin, and HOMA-IR levels were significantly higher in the obese group (both p<0.001). Total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride levels were significantly higher in the obese group (p<0.001). TAS (med: 2.5 μmol Trolox eq/L (1.7–3.3)) and TOS (med: 49.1 μmol H2O2 eq/L (34.5–78.8)) levels and TTL (med: 0.22 mmol/L (0.16–0.26)) were significantly higher in the obese group (p=0.001). CRP levels showed positive correlation with TOS and negative correlation with TTL levels (p=0.005, r=0.473; p=0.01, r=−0.417; respectively). TTL levels exhibited negative correlation with TOS levels (p=0.03, r=−0.347). Conclusions In conclusion, obese children were exposed to more oxidative burden than children with normal weight. Increased systemic oxidative stress induced by childhood obesity can cause development of obesity-related complications and diseases. Widely focussed studies are required on the use of oxidative parameters as early prognostic parameters in detection of obesity-related complications.
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Affiliation(s)
- Elif Kilic
- Department of Biochemistry, Bezmialem Vakif University, Medical Faculty, Istanbul, Turkey
| | - Ömer Faruk Özer
- Department of Biochemistry, Bezmialem Vakif University, Medical Faculty, Istanbul, Turkey
| | - Aybala Erek Toprak
- Department of Biochemistry, Medeniyet University, Medical Faculty, Istanbul, Turkey
| | - Hayriye Erman
- Department of Biochemistry, Medeniyet University, Medical Faculty, Istanbul, Turkey
| | - Emel Torun
- Department of Paediatrics, Bezmialem Vakif University, Medical Faculty, Istanbul, Turkey
| | - Sıddıka Kesgin Ayhan
- Department of Biochemistry, Bezmialem Vakif University, Medical Faculty, Istanbul, Turkey
| | - Hifa Gülru Caglar
- Department of Biochemistry, Bezmialem Vakif University, Medical Faculty, Istanbul, Turkey
| | - Sahbettin Selek
- Department of Biochemistry, Bezmialem Vakif University, Medical Faculty, Istanbul, Turkey
| | - Abdurrahim Kocyigit
- Department of Biochemistry, Bezmialem Vakif University, Medical Faculty, Istanbul, Turkey
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Fotbolcu H, Zorlu E. Nonalcoholic fatty liver disease as a multi-systemic disease. World J Gastroenterol 2016; 22:4079-4090. [PMID: 27122660 PMCID: PMC4837427 DOI: 10.3748/wjg.v22.i16.4079] [Citation(s) in RCA: 76] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Revised: 02/02/2016] [Accepted: 03/02/2016] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD includes a wide spectrum of liver conditions ranging from simple steatosis to nonalcoholic steatohepatitis and advanced hepatic fibrosis. NAFLD has been recognized as a hepatic manifestation of metabolic syndrome linked with insulin resistance. NAFLD should be considered not only a liver specific disease but also an early mediator of systemic diseases. Therefore, NAFLD is usually associated with cardiovascular disease, chronic kidney disease, type 2 diabetes, obesity, and dyslipidemia. NAFLD is highly prevalent in the general population and is associated with increased cardiovascular morbidity and mortality. The underlying mechanisms and pathogenesis of NAFLD with regard to other medical disorders are not yet fully understood. This review focuses on pathogenesis of NAFLD and its relation with other systemic diseases.
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Nabavi S, Rafraf M, Somi MH, Homayouni-Rad A, Asghari-Jafarabadi M. Probiotic yogurt improves body mass index and fasting insulin levels without affecting serum leptin and adiponectin levels in non-alcoholic fatty liver disease (NAFLD). J Funct Foods 2015. [DOI: 10.1016/j.jff.2015.08.031] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
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LEGHI GE, DOMENICI FA, VANNUCCHI H. INFLUENCE OF OXIDATIVE STRESS AND OBESITY IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS. ARQUIVOS DE GASTROENTEROLOGIA 2015; 52:228-33. [DOI: 10.1590/s0004-28032015000300014] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Accepted: 05/08/2015] [Indexed: 12/11/2022]
Abstract
BackgroundNonalcoholic steatohepatitis is considered the hepatic manifestation of metabolic syndrome and it is particularly associated to the insulin resistance, hypertension, obesity and abnormalities in lipid and glucose metabolism.ObjectiveConsidering the importance of obesity and oxidative stress in the pathophysiology of nonalcoholic steatohepatitis, this study aimed to evaluate the presence and association of the obesity and oxidative stress in this pathology.MethodsFifteen outpatients with nonalcoholic steatohepatitis (nonalcoholic steatohepatitis group), diagnosed according to the histopathological findings from the liver biopsy, and 15 body mass index-matched subjects (non nonalcoholic steatohepatitis group) without nonalcoholic steatohepatitis were included. All volunteers were registered in a Brazilian University Hospital. Nutritional assessment (weight, height, body mass index and waist circumference) and biochemical analysis (fasting glucose, liver enzymes, lipid profile, leptin, superoxide dismutase, glutathione peroxidase, vitamins C and E, catalase and 8-isoprostane) were performed for all the participants. The student t test was used for statistical analysis, with P<0.05 as the significant factor.ResultsNonalcoholic steatohepatitis patients had higher fasting glucose, hepatic enzymes (serum aspartate aminotransaminase, alanine aminotransaminase, gamma glutamyl transferase, alkaline phosphatase), triglycerides and superoxide dismutase and lower glutathione peroxidase values than non nonalcoholic steatohepatitis individuals.ConclusionThis paper demonstrates that only the presence of obesity is not enough to trigger alterations in all the studied biomarkers. Despite the majority of oxidative stress markers being found to be similar in both conditions, the nonalcoholic steatohepatitis subjects could be slightly more affected than the non nonalcoholic steatohepatitis individuals.
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Polimeni L, Del Ben M, Baratta F, Perri L, Albanese F, Pastori D, Violi F, Angelico F. Oxidative stress: New insights on the association of non-alcoholic fatty liver disease and atherosclerosis. World J Hepatol 2015; 7:1325-1336. [PMID: 26052378 PMCID: PMC4450196 DOI: 10.4254/wjh.v7.i10.1325] [Citation(s) in RCA: 148] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Revised: 12/01/2014] [Accepted: 03/16/2015] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseases ranging from simple fatty liver to non-alcoholic steatohepatitis (NASH), which may progress to fibrosis and more severe liver complications such as cirrhosis, hepatocellular carcinoma and liver mortality. NAFLD is strongly associated with obesity, insulin resistance, hypertension, and dyslipidaemia, and is now regarded as the liver manifestation of the metabolic syndrome. The increased mortality of patients with NAFLD is primarily a result of cardiovascular disease and, to a lesser extent, to liver related diseases. Increased oxidative stress has been reported in both patients with NAFLD and patient with cardiovascular risk factors. Thus, oxidative stress represents a shared pathophysiological disorder between the two conditions. Several therapeutic strategies targeting oxidative stress reduction in patients with NAFLD have been proposed, with conflicting results. In particular, vitamin E supplementation has been suggested for the treatment of non-diabetic, non-cirrhotic adults with active NASH, although this recommendation is based only on the results of a single randomized controlled trial. Other antioxidant treatments suggested are resveratrol, silybin, L-carnitine and pentoxiphylline. No trial so far, has evaluated the cardiovascular effects of antioxidant treatment in patients with NAFLD. New, large-scale studies including as end-point also the assessment of the atherosclerosis markers are needed.
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Affiliation(s)
- Licia Polimeni
- Licia Polimeni, Francesco Angelico, Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy
| | - Maria Del Ben
- Licia Polimeni, Francesco Angelico, Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy
| | - Francesco Baratta
- Licia Polimeni, Francesco Angelico, Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy
| | - Ludovica Perri
- Licia Polimeni, Francesco Angelico, Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy
| | - Fabiana Albanese
- Licia Polimeni, Francesco Angelico, Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy
| | - Daniele Pastori
- Licia Polimeni, Francesco Angelico, Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy
| | - Francesco Violi
- Licia Polimeni, Francesco Angelico, Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy
| | - Francesco Angelico
- Licia Polimeni, Francesco Angelico, Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy
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Khan UI, McGinn AP, Isasi CR, Groisman-Perelstein A, Diamantis PM, Ginsberg M, Wylie-Rosett J. Differences in Cardiometabolic Risk between Insulin-Sensitive and Insulin-Resistant Overweight and Obese Children. Child Obes 2015; 11:289-96. [PMID: 25774664 PMCID: PMC4485365 DOI: 10.1089/chi.2014.0112] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND It is known that 15-30% overweight/obese adults do not suffer cardiometabolic consequences. There is limited literature examining factors that can be used to assess cardiometabolic health in overweight/obese children. If such factors can be identified, they would aid in differentiating those most in need for aggressive management. METHODS Baseline data from 7- to 12-year-old, overweight, and obese children enrolled in a weight management program at an urban hospital were analyzed. Homeostatic model assessment for insulin resistance (HOMA-IR) <2.6 was used to define insulin-sensitive and HOMA-IR ≥2.6 was used to defined insulin-resistant participants. Demographics, physical activity measures, and cardiometabolic risk factors were compared between the two phenotypes. Odds ratios (ORs) examining the association between intermediate endpoints (metabolic syndrome [MetS], nonalcoholic fatty liver disease [NAFLD], systemic inflammation, and microalbuminuria) and the two metabolic phenotypes were evaluated. RESULTS Of the 362 overweight/obese participants, 157 (43.5%) were insulin sensitive and 204 (56.5%) were insulin resistant. Compared to the insulin-sensitive group, the insulin-resistant group was older (8.6±1.6 vs. 9.9±1.7; p<0.001) and had a higher BMI z-score (1.89±0.42 vs. 2.04±0.42; p=0.001). After multivariable adjustment, compared to the insulin-sensitive group, the insulin-resistant group had higher odds of having MetS (OR, 5.47; 95% confidence interval [CI]: 1.72, 17.35; p=0.004) and NAFLD (OR, 8.66; 95% CI, 2.48, 30.31; p=0.001), but not systemic inflammation (OR, 1.06; 95% CI: 0.56, 2.03; p=0.86) or microalbuminuria (OR, 1.71; 95% CI, 0.49, 6.04; p=0.403). CONCLUSIONS Using a HOMA-IR value of ≥2.6, clinical providers can identify prepubertal and early pubertal children most at risk. Focusing limited resources on aggressive weight interventions may lead to improvement in cardiometabolic health.
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Affiliation(s)
- Unab I. Khan
- Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY
- Department of Family and Social Medicine, Albert Einstein College of Medicine, Bronx, NY
| | - Aileen P. McGinn
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY
| | - Carmen R. Isasi
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY
| | | | | | - Mindy Ginsberg
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY
| | - Judith Wylie-Rosett
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY
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Yin X, Huang Y, Jung DW, Chung HC, Choung SY, Shim JH, Kang IJ. Anti-Diabetic Effect of Aster sphathulifolius in C57BL/KsJ-db/db Mice. J Med Food 2015; 18:987-98. [PMID: 25961463 DOI: 10.1089/jmf.2014.3416] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
In this study, we investigated the anti-diabetic effect of Aster sphathulifolius (AS) extract in C57BL/KsJ-db/db mice. The db/db mice were orally administered with AS 50% ethanol extract at concentrations of 50, 100, and 200 mg/kg/day (db/db-AS50, db/db-AS100, and db/db-AS200, respectively) for 10 weeks. Food and water intake, fasting blood glucose concentrations, blood glycosylated hemoglobin levels, and plasma insulin levels were significantly lower in the db/db-AS200 group than in the vehicle-treated db/db group; whereas glucose tolerance was significantly improved in the db/db-AS200 group. Moreover, AS dose dependently increased both insulin receptor substrate 1 and glucose transporter type 4 expression in skeletal muscle, significantly increased glucokinase expression, and decreased glucose 6-phosphatase and phosphoenolpyruvate carboxykinase expressions in the liver. The expressions of transcription factors, such as sterol-regulatory element-binding protein, peroxisome proliferator-activated receptor γ, and adipocyte protein 2, were upregulated in adipose tissue. Furthermore, immunohistochemical analysis showed that AS upregulated insulin production by increasing pancreatic β-cell mass. In summary, AS extract normalized hyperglycemia by multiple mechanisms: inhibition of glyconeogenesis, acceleration of glucose metabolism and lipid metabolism, and increase of glucose uptake. Using in vivo assays, this study has shown the potential of AS as a medicinal food and suggests the efficacy of AS for the use of prevention of diabetes.
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Affiliation(s)
- Xingfu Yin
- 1 Department of Food Science and Nutrition, Hallym University , Gwangwon, Korea
| | - Yuhua Huang
- 1 Department of Food Science and Nutrition, Hallym University , Gwangwon, Korea
| | - Da-Woon Jung
- 1 Department of Food Science and Nutrition, Hallym University , Gwangwon, Korea
| | | | - Se Young Choung
- 3 Department of Preventive Pharmacy and Toxicology, College of Pharmacy, Kyung Hee University , Seoul, Korea
| | - Jae-Hoon Shim
- 1 Department of Food Science and Nutrition, Hallym University , Gwangwon, Korea
| | - Il-Jun Kang
- 1 Department of Food Science and Nutrition, Hallym University , Gwangwon, Korea
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Pirgon Ö, Sandal G, Gökçen C, Bilgin H, Dündar B. Social anxiety, depression and self-esteem in obese adolescent girls with acanthosis nigricans. J Clin Res Pediatr Endocrinol 2015; 7:63-8. [PMID: 25800478 PMCID: PMC4439894 DOI: 10.4274/jcrpe.1515] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
OBJECTIVE To assess the impact of acanthosis nigricans (AN) on depression symptoms, related quality of life and self-esteem scores in obese adolescent girls. METHODS Fifty-nine obese adolescent girls (mean age: 13.19±1.3 years, age range: 12-17 years, mean body mass index: 29.89±3.30) were enrolled in this study. The obese adolescent girls were divided into two groups based on presence or absence of AN. Non-obese healthy adolescents constituted the control group (30 girls, mean age: 13.5±1.4 years). All subjects were evaluated using the Children's Depression Inventory (CDI), the State-Trait Anxiety Inventory for Children (STAI-C), and the modified Rosenberg Self-Esteem Scale (SES). Higher scores indicated more severe depression and anxiety, as well as low self-esteem status. RESULTS The AN and non-AN obese groups showed significantly higher CDI, STAI-C and SES scores than the control group, and the two obese groups demonstrated no significant differences for these scores. The AN obese group with higher total testosterone levels (>50 ng/dL) had higher scores for SES (2.55±1.8 vs. 1.42±1.2; p=0.03) than the AN obese group with low total testosterone levels. SES scores significantly correlated with total testosterone levels (r=0.362; p=0.03) and fasting insulin (r=0.462; p=0.03) in the AN obese group. CONCLUSION Higher SES scores (low self-esteem status) were determined in obese adolescents with acanthosis and were related to hyperandrogenism. This study also showed that a high testosterone level may be one of the important indicators of low self-esteem status in obese girls with AN.
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Affiliation(s)
- Özgür Pirgon
- Süleyman Demirel University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, Isparta, Turkey. E-mail:
| | - Gonca Sandal
- Süleyman Demirel University Faculty of Medicine, Department of Neonatology, Isparta, Turkey
| | - Cem Gökçen
- Gaziantep University Faculty of Medicine, Department of Child and Adolescent Psychiatry, Gaziantep, Turkey
| | - Hüseyin Bilgin
- Konya Training and Research Hospital, Clinic of Pediatrics, Konya, Turkey
| | - Bumin Dündar
- Katip Çelebi University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, Izmir, Turkey
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Liu J, Xu Y, Hu Y, Wang G. The role of fibroblast growth factor 21 in the pathogenesis of non-alcoholic fatty liver disease and implications for therapy. Metabolism 2015; 64:380-90. [PMID: 25516477 DOI: 10.1016/j.metabol.2014.11.009] [Citation(s) in RCA: 89] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2014] [Revised: 10/06/2014] [Accepted: 11/25/2014] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) includes a cluster of liver disorders ranging from simple fatty liver to non-alcoholic steatohepatitis (NASH) and cirrhosis. Due to its liver and vascular complications, NAFLD has become a public health problem with high morbidity and mortality. The pathogenesis of NAFLD is considered a "multi-hit hypothesis" that involves lipotoxicity, oxidative stress, endoplasmic reticulum stress, a chronic inflammatory state and mitochondrial dysfunction. Fibroblast growth factor 21 (FGF21) is a member of the fibroblast growth factor family with multiple metabolic functions. FGF21 directly regulates lipid metabolism and reduces hepatic lipid accumulation in an insulin-independent manner. Several studies have shown that FGF21 can ameliorate the "multi-hits" in the pathogenesis of NAFLD. The administration of FGF21 reverses hepatic steatosis, counteracts obesity and alleviates insulin resistance in rodents and nonhuman primates. Using several strategies, we show that the reversal of simple fatty liver and NASH is mediated by activation of the FGF21 signaling pathway. In this review, we describe the molecular mechanisms involved in the onset and/or progression of NAFLD, and review the current literature to highlight the therapeutic procedures associated with the FGF21 signaling pathway for simple fatty liver and NASH, which are the two most important types of NAFLD.
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Affiliation(s)
- Jia Liu
- Department of Endocrinology, Beijing Chao-yang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang District, Beijing 100020, China
| | - Yuan Xu
- Department of Endocrinology, Beijing Chao-yang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang District, Beijing 100020, China
| | - Yanjin Hu
- Department of Endocrinology, Beijing Chao-yang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang District, Beijing 100020, China
| | - Guang Wang
- Department of Endocrinology, Beijing Chao-yang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang District, Beijing 100020, China.
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Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition characterized by insulin resistance, type 2 diabetes and fat accumulation in the liver that may cause hepatic inflammation and progressive scarring leading to nonalcoholic steatohepatitis (NASH) and irreversible liver damage (cirrhosis). As a result, there has been increased recognition of the need to assess and closely monitor individuals for risk factors of components of NAFLD and NASH, as well as the severity of these conditions using biomarkers. AIM To review the biomarkers used to diagnose and define the severity of NAFLD and NASH. METHODS A comprehensive PubMed and Google Scholar literature search was performed using the terms "non-alcoholic fatty liver disease", "non-alcoholic steatohepatitis", as well as the name of each biomarker known to be used. Articles indexed between 2004 and 2014 were used. Each author read the publications separately and the results were discussed. RESULTS Biomarkers offer a potential prognostic or diagnostic indicator for disease manifestation, progression or both. Serum biomarkers, including total cholesterol, triglycerides, insulin resistance and C-peptide, have been used for many years. Emerging biomarkers, such as apolipoprotein A1, apolipoprotein B, leptin, adiponectin, free fatty acids, ghrelin and tumour necrosis factor-alpha, have been proposed as tools that could provide valuable complementary information to that obtained from traditional biomarkers. Moreover, markers of cell death and mitochondrial dysfunction (cytokeratins) represent powerful predictors of risk. For biomarkers to be clinically useful in accurately diagnosing and treating disorders, age-specific reference intervals that account for differences in sex and ethnic origin are a necessity. CONCLUSIONS The present review attempts to provide a comprehensive analysis of the emerging risk biomarkers of NAFLD and NASH, and to use the clinical significance and analytical considerations of each biomarker pointing out sentinel features of disease progression.
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Ibarra-Reynoso LDR, Pisarchyk L, Pérez-Luque EL, Garay-Sevilla ME, Malacara JM. Whole-body and hepatic insulin resistance in obese children. PLoS One 2014; 9:e113576. [PMID: 25411786 PMCID: PMC4239088 DOI: 10.1371/journal.pone.0113576] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2014] [Accepted: 10/25/2014] [Indexed: 12/11/2022] Open
Abstract
Background Insulin resistance may be assessed as whole body or hepatic. Objective To study factors associated with both types of insulin resistance. Methods Cross-sectional study of 182 obese children. Somatometric measurements were registered, and the following three adiposity indexes were compared: BMI, waist-to-height ratio and visceral adiposity. Whole-body insulin resistance was evaluated using HOMA-IR, with 2.5 as the cut-off point. Hepatic insulin resistance was considered for IGFBP-1 level quartiles 1 to 3 (<6.67 ng/ml). We determined metabolite and hormone levels and performed a liver ultrasound. Results The majority, 73.1%, of obese children had whole-body insulin resistance and hepatic insulin resistance, while 7% did not have either type. HOMA-IR was negatively associated with IGFBP-1 and positively associated with BMI, triglycerides, leptin and mother's BMI. Girls had increased HOMA-IR. IGFBP-1 was negatively associated with waist-to-height ratio, age, leptin, HOMA-IR and IGF-I. We did not find HOMA-IR or IGFBP-1 associated with fatty liver. Conclusion In school-aged children, BMI is the best metric to predict whole-body insulin resistance, and waist-to-height ratio is the best predictor of hepatic insulin resistance, indicating that central obesity is important for hepatic insulin resistance. The reciprocal negative association of IGFBP-1 and HOMA-IR may represent a strong interaction of the physiological processes of both whole-body and hepatic insulin resistance.
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Affiliation(s)
| | - Liudmila Pisarchyk
- Department of Medical Sciences, University of Guanajuato, Campus León, 20 de Enero 929, León Guanajuato, México
| | - Elva Leticia Pérez-Luque
- Department of Medical Sciences, University of Guanajuato, Campus León, 20 de Enero 929, León Guanajuato, México
| | - Ma. Eugenia Garay-Sevilla
- Department of Medical Sciences, University of Guanajuato, Campus León, 20 de Enero 929, León Guanajuato, México
- * E-mail:
| | - Juan Manuel Malacara
- Department of Medical Sciences, University of Guanajuato, Campus León, 20 de Enero 929, León Guanajuato, México
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Effects of Soothing Liver and Invigorating Spleen Recipe on Lipid Metabolism Disorders in Kupffer Cells of NAFLD Rats by LXRα/SREBP-1c Signal Pathway. CHINESE HERBAL MEDICINES 2014. [DOI: 10.1016/s1674-6384(14)60045-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
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Della Corte C, Liccardo D, Ferrari F, Alisi A, Nobili V. Current pharmacotherapy for treating pediatric nonalcoholic fatty liver disease. Expert Opin Pharmacother 2014; 15:2501-11. [DOI: 10.1517/14656566.2014.960389] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Wang XG, Han M, Zhang LD, Wu GX, Ding H, Zhang B, Huang LH. Regulatory effect of hydrogen sulfide on β oxidation in fatty liver in rats. Shijie Huaren Xiaohua Zazhi 2014; 22:3791-3795. [DOI: 10.11569/wcjd.v22.i25.3791] [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] [Indexed: 02/06/2023] Open
Abstract
AIM: To observe the regulatory effect of hydrogen sulfide on β oxidation in fatty liver in rats.
METHODS: Eighteen male SD rats were randomly divided into a normal control group, a high-fat diet group and a high-fat diet + NaHS group. High-fat diet was ordinary diet supplemented with 2% cholesterol and 18% lard. The high-fat diet + NaHS group was given a high-fat diet and intraperitoneal injection of 400 mmol/L sodium hydrosulfide solution (5 mL/kg). Eight weeks after treatment, the animals were killed. The content of ketones and enoyl-CoA hydratase activity in liver homogenates were measured, and pathological changes in the liver were observed.
RESULTS: After 8 wk of treatment, fatty liver was successfully induced. Application of sodium hydrosulfide reduced fatty liver significantly. Intrahepatic triglyceride and cholesterol significantly increased in the high-fat diet group compared with the normal control group (3.87 mmol/L ± 2.63 mmol/L vs 1.18 mmol/L ± 0.85 mmol/L, 5.00 mmol/L ± 1.01 mmol/L vs 2.61 mmol/L ± 0.33 mmol/L), while treatment with sodium hydrosulfide significantly reduced hepatic lipid composition (2.28 mmol/L ± 0.51 mmol/L vs 3.87 ± 2.63 mmol/L, 4.50 mmol/L ± 1.25 mmol/L vs 5.00 mmol/L ± 1.01 mmol/L). Compared with the normal control group, hydrogen sulfide content in the high-fat diet group was significantly reduced (14.00 µmol/L ± 6.21 µmol/L vs 20.20 µmol/L ± 11.90 µmol/L); however, application of sodium hydrosulfide significantly increased hydrogen sulfide content (48.20 µmol/L ± 8.50 µmol/L vs 14.00 µmol/L ± 6.21 µmol/L). Compared with the control animals, the liver enoyl-CoA activity was significantly reduced in the high-fat diet group (25.0 µmol/min ± 7.7 µmol/min vs 12.6 µmol/min ± 3.1 µmol/min), by up to 50%, while sodium hydrosulfide significantly increased enoyl-CoA activity (19.9 µmol/min ± 6.0 µmol/min vs 12.6 µmol/min ± 3.1 µmol/min), by 60%. Hydrogen sulfide content was negatively correlated with TG and TC in the high-fat diet group (r = -0.621, -0.432, P = 0.01036, 0.04497), but positively correlated with enoyl-CoA hydratase activity (r = 0.513, P = 0.00833).
CONCLUSION: Hydrogen sulfide promotes β oxidation and reduces fat accumulation in fatty liver in rats.
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Eren E, Abuhandan M, Solmaz A, Taşkın A. Serum paraoxonase/arylesterase activity and oxidative stress status in children with metabolic syndrome. J Clin Res Pediatr Endocrinol 2014; 6:163-8. [PMID: 25241610 PMCID: PMC4293645 DOI: 10.4274/jcrpe.1454] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVE This study aimed to measure paraoxonase/arylesterase activities and to evaluate the total oxidant and antioxidant capacities in obese children and in children with metabolic syndrome (MetS). METHODS A total of 151 children of comparable ages (13.23±1.96 years, 13.45±1.85 years and 13.95±1.31 years) were enrolled in the study. Forty of these were children with MetS, 55 were obese and 56 were healthy controls. Diagnosis of the MetS was made according to International Diabetes Federation criteria. Paraoxonase/arylesterase activities were evaluated by using paraoxon and phenylacetate substrates. Total oxidant status (TOS) and total antioxidant status (TAS) were measured and oxidative stress index (OSI) was estimated by calculation. RESULTS High levels of paraoxonase were detected in the obese group, whereas high levels of arylesterase were detected in both MetS and obese groups. Higher values for TOS, TAS and OSI were found in the MetS group (p<0.05). CONCLUSION Higher values of mean TOS and OSI in the MetS group than those in the control groups indicate that these parameters may be indicators of future risks such as atherosclerosis in patients with MetS.
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Affiliation(s)
- Erdal Eren
- Uludağ University, Faculty of Medicine, Department of Pediatric Endocrinology, Bursa, Turkey. E-ma-il:
| | - Mahmut Abuhandan
- Harran University, Faculty of Medicine, Department of Pediatrics, Şanlıurfa, Turkey
| | - Abdullah Solmaz
- Harran University, Faculty of Medicine, Department of Pediatrics, Şanlıurfa, Turkey
| | - Abdullah Taşkın
- Harran University, Faculty of Medicine, Department of Biochemistry, Şanlıurfa, Turkey
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Ben MD, Polimeni L, Baratta F, Pastori D, Loffredo L, Angelico F. Modern approach to the clinical management of non-alcoholic fatty liver disease. World J Gastroenterol 2014; 20:8341-8350. [PMID: 25024593 PMCID: PMC4093688 DOI: 10.3748/wjg.v20.i26.8341] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2013] [Revised: 11/05/2013] [Accepted: 03/07/2014] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common and emerging form of chronic liver disease worldwide. It includes a wide spectrum of liver diseases ranging from simple fatty liver to steatohepatitis, which may progress to cirrhosis, liver cancer, and liver mortality. Common metabolic diseases, which are well established cardiovascular risk factors, have been associated to NAFLD and cardiovascular disease is the single most important cause of morbidity and mortality in this patient population. The pathogenesis of NAFLD appears multifactorial and many mechanisms have been proposed as possible causes of fatty liver infiltration. Management of fatty liver has become a major challenge to healthcare systems as the consequence of the increasing rates of obesity worldwide. First-line management focuses on lifestyle modifications. Moderate weight reduction either by dietary restriction or by increased habitual physical activity is safe and highly recommended. Several therapeutic interventions have been proposed. These include insulin sensitizer agents, lipid lowering drugs, antioxidants such as vitamin E and supplementation of vitamin D3. However, therapeutic strategies have been largely empirical so far, and experimental trials have mostly been carried out in uncontrolled settings with small sample sizes. Metabolic conditions such as diabetes mellitus, obesity, hypertension and hyperlipidemia, should be strongly considered and a multidisciplinary approach should be personalized for individual patients. Treatment of co-morbidities should be regarded as of paramount importance in the management of these patients. The purpose of this review is to examine different approaches for the clinical management of non-alcoholic fatty liver disease.
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Del Ben M, Polimeni L, Carnevale R, Bartimoccia S, Nocella C, Baratta F, Loffredo L, Pignatelli P, Violi F, Angelico F. NOX2-generated oxidative stress is associated with severity of ultrasound liver steatosis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol 2014; 14:81. [PMID: 24758604 PMCID: PMC4014405 DOI: 10.1186/1471-230x-14-81] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2013] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Chronic oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. However, so far, few studies reported increased circulating levels of oxidative stress markers in patients with non-alcoholic fatty liver and no study has been performed with newer markers of systemic oxidative stress. The aim was to assess the relationship between urinary 8-iso-prostaglandin F2α and serum soluble NOX2-derived peptide and the severity of liver steatosis in subjects with non-alcoholic fatty liver. METHODS The study was performed in 264 consecutive patients referred for suspected metabolic disease. Steatosis was defined according to Hamaguchi ultrasonographic criteria. Oxidative stress was assessed by urinary 8-iso- prostaglandin F2α and serum soluble NOX2-derived peptide levels. RESULTS Patients with non-alcoholic fatty liver had higher (p < 0.001) mean values of urinary 8-iso-PGF2α and of serum soluble NOX2-derived peptide, alanine aminotransferase, Cytokeratin-18 and homeostasis model of insulin resistance and lower values of serum adiponectin as compared to those without. Prevalence of metabolic syndrome and of its clinical features was significantly higher in patients with non-alcoholic fatty liver. Same findings were also observed after the exclusion of obese subjects, or subjects with diabetes or with metabolic syndrome and in those not taking statin medication. In addition, the levels of urinary 8-iso-PGF2α were independent predictors of non-alcoholic fatty liver and a strong association of urinary 8-iso-PGF2α and of serum soluble NOX2-derived peptide with the severity of steatosis at ultrasound was also observed. CONCLUSIONS We demonstrated increased markers of oxidative stress in subjects with non-alcoholic fatty liver. Urinary 8-iso-PGF2α and serum soluble NOX2-derived peptide levels were independent from obesity, diabetes and metabolic syndrome and increased with the severity of liver steatosis at ultrasound.
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Affiliation(s)
- Maria Del Ben
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - Licia Polimeni
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - Roberto Carnevale
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - Simona Bartimoccia
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - Cristina Nocella
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - Francesco Baratta
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - Lorenzo Loffredo
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - Pasquale Pignatelli
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - Francesco Violi
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - Francesco Angelico
- Department of Public Health and Infectious Disease, Sapienza University, Rome, Italy
- I Clinica Medica – Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy
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Rupérez AI, Gil A, Aguilera CM. Genetics of oxidative stress in obesity. Int J Mol Sci 2014; 15:3118-44. [PMID: 24562334 PMCID: PMC3958901 DOI: 10.3390/ijms15023118] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Revised: 02/12/2014] [Accepted: 02/12/2014] [Indexed: 12/18/2022] Open
Abstract
Obesity is a multifactorial disease characterized by the excessive accumulation of fat in adipose tissue and peripheral organs. Its derived metabolic complications are mediated by the associated oxidative stress, inflammation and hypoxia. Oxidative stress is due to the excessive production of reactive oxygen species or diminished antioxidant defenses. Genetic variants, such as single nucleotide polymorphisms in antioxidant defense system genes, could alter the efficacy of these enzymes and, ultimately, the risk of obesity; thus, studies investigating the role of genetic variations in genes related to oxidative stress could be useful for better understanding the etiology of obesity and its metabolic complications. The lack of existing literature reviews in this field encouraged us to gather the findings from studies focusing on the impact of single nucleotide polymorphisms in antioxidant enzymes, oxidative stress-producing systems and transcription factor genes concerning their association with obesity risk and its phenotypes. In the future, the characterization of these single nucleotide polymorphisms (SNPs) in obese patients could contribute to the development of controlled antioxidant therapies potentially beneficial for the treatment of obesity-derived metabolic complications.
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Affiliation(s)
- Azahara I Rupérez
- Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology, Centre for Biomedical Research, University of Granada, 18100 Armilla, Granada, Spain
| | - Angel Gil
- Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology, Centre for Biomedical Research, University of Granada, 18100 Armilla, Granada, Spain
| | - Concepción M Aguilera
- Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology, Centre for Biomedical Research, University of Granada, 18100 Armilla, Granada, Spain.
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Tsukahara H. Oxidative Stress Biomarkers in Pediatric Medicine – A 2013 Update. SYSTEMS BIOLOGY OF FREE RADICALS AND ANTIOXIDANTS 2014:689-715. [DOI: 10.1007/978-3-642-30018-9_36] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Illnait J, Rodríguez I, Mendoza S, Fernández Y, Mas R, Miranda M, Piñera J, Fernández JC, Mesa M, Fernández L, Carbajal D, Gámez R. Effects of D-002, a mixture of high molecular weight beeswax alcohols, on patients with nonalcoholic fatty liver disease. Korean J Intern Med 2013; 28:439-48. [PMID: 23864802 PMCID: PMC3712152 DOI: 10.3904/kjim.2013.28.4.439] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2012] [Revised: 03/14/2013] [Accepted: 05/10/2013] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND/AIMS Nonalcoholic fatty liver disease (NAFLD) is intimately related to insulin resistance and ranges from a benign course to liver fibrosis and cirrhosis. NAFLD management mainly involves dietary modification and weight loss. Although no fully successful pharmacological intervention is available, alternative therapies to treat NAFLD have shown promising results. Experimental studies have shown that D-002, a mixture of beeswax alcohols with antioxidant effects, is hepatoprotective. The aim of this study was to investigate the efficacy and safety of D-002 in patients with NALFD. METHODS Fifty patients with NAFLD were randomized to receive a placebo or D-002 (100 mg/day) for 24 weeks. The primary endpoint was a significant ultrasonography-detected reduction of liver fat infiltration versus a placebo. Secondary endpoints were decreases in the homeostatic model assessment (HOMA) index, insulin levels, serum liver enzymes, increases in plasma total antioxidant status (TAS) and improved clinical symptoms versus the placebo recipients. RESULTS At randomization, all indicators were comparable in both groups. At study completion, seven (28.0%) D-002-patients, but none of the placebo recipients, exhibited a normal liver echo pattern on ultrasonography (p < 0.01). Also, D-002 significantly reduced (p < 0.01 vs. baseline and placebo) the HOMA index and insulin levels and increased the TAS, but did not affect other parameters. The proportion of D-002-patients (12/25, 48.0%) showing symptom improvement was higher (p < 0.001) than that of the placebo group (1/25, 4.0%). The treatment was safe and well tolerated. Three patients in each group withdrew from the study. CONCLUSIONS D-002 (100 mg/day) improved ultrasonographic findings, indicators of insulin resistance, plasma TAS and clinical evolution on NAFLD patients. Further studies, however, are needed to confirm these results.
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Affiliation(s)
- José Illnait
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
| | - Iván Rodríguez
- Surgical Medical Research Centre, National Centre for Scientific Research, Havana, Cuba
| | - Sarahí Mendoza
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
| | - Yolanda Fernández
- Surgical Medical Research Centre, National Centre for Scientific Research, Havana, Cuba
| | - Rosa Mas
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
| | - Mirtha Miranda
- Surgical Medical Research Centre, National Centre for Scientific Research, Havana, Cuba
| | - Jesús Piñera
- Surgical Medical Research Centre, National Centre for Scientific Research, Havana, Cuba
| | | | - Meilis Mesa
- Surgical Medical Research Centre, National Centre for Scientific Research, Havana, Cuba
| | - Lilia Fernández
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
| | - Daisy Carbajal
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
| | - Rafael Gámez
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
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