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1
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Köpsel M, Kostka T, Rodriguez-Werner M, Esatbeyoglu T. The influence of fruit juice extracts on glucose intestinal transporters and antioxidant genes in a Caco-2 and HT29-MTX co-culture cell system. Food Funct 2025; 16:1423-1441. [PMID: 39895307 DOI: 10.1039/d4fo03950e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2025]
Abstract
In recent years, the interest of consumers in fruit juice extracts as nutraceuticals has increased. Fruits, especially red berries, contain valuable bioactive compounds such as polyphenols. Polyphenols are often associated with anti-oxidant, anti-inflammatory, anti-diabetic, anti-cancer, cardioprotective and gastroprotective properties. However, the relationship between the various effects of fruit juice extracts and their influence on the permeability of the intestinal barrier, as well as their influence on glucose transport across the intestinal membrane, is not known. Therefore, in the present study, anthocyanins and copigments were obtained from 11 fruit juice extracts by XAD7 column chromatography and characterized their health-promoting effects, as well as their influence on the intestinal membrane. Chokeberry, pomegranate and blueberry extracts showed the highest antioxidant activity, but showed incomplete regeneration of the intestinal membrane upon treatment-induced higher permeability. This may depended on the high anthocyanin level of these extracts. Treatments with gojiberry extract, elderberry extract and the copigment fraction of apple achieved the best suitable regeneration of the intestinal barrier. The transcription of epithelial glucose transporters GLUT1 und GLUT2 as well as for the oxidative stress genes catalase (CAT) and superoxide dismutase (SOD) were most effectively reduced by chokeberry extract. To sum up, fruit juice extracts possess high antioxidant potentials and can reduce the expression of antioxidant enzymes and glucose transporters in colon cells. While the glucose uptake may be reduced, the intestinal permeability is increased, which varies due to the extract composition. Therefore, fruit juice extracts need to be fractionated and characterized in more detail to identify the health-beneficial compounds.
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Affiliation(s)
- Magdalena Köpsel
- Department of Molecular Food Chemistry and Food Development, Institute of Food and One Health, Gottfried Wilhelm Leibniz University Hannover, Am Kleinen Felde 30, 30167 Hannover, Germany.
| | - Tina Kostka
- Department of Molecular Food Chemistry and Food Development, Institute of Food and One Health, Gottfried Wilhelm Leibniz University Hannover, Am Kleinen Felde 30, 30167 Hannover, Germany.
- Division of Food Chemistry and Toxicology, Department of Chemistry, RPTU Kaiserslautern-Landau, Erwin-Schrödinger-Strasse 52, 67663 Kaiserslautern, Germany.
| | | | - Tuba Esatbeyoglu
- Department of Molecular Food Chemistry and Food Development, Institute of Food and One Health, Gottfried Wilhelm Leibniz University Hannover, Am Kleinen Felde 30, 30167 Hannover, Germany.
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2
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Zhang Y, Zhai Y, Wei X, Yang X, Deng C, Li Q, Wang W, Hao R. Effects of grape seed procyanidins on the lipid metabolism of growing-finishing pigs based on transcriptomics and metabolomics analyses. Meat Sci 2024; 213:109504. [PMID: 38555738 DOI: 10.1016/j.meatsci.2024.109504] [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: 06/26/2023] [Revised: 03/23/2024] [Accepted: 03/27/2024] [Indexed: 04/02/2024]
Abstract
This study investigated how lipid metabolism in the longissimus thoracis is influenced by the diet supplemented with grape seed procyanidins (GSPs) in growing-finishing pigs. Forty-eight crossbred pigs were randomly assigned to four groups, each receiving a basal diet, or basal diet added with 150, 200, and 250 mg/kg GSPs. Transcriptomics and metabolomics were employed to explore differential gene and metabolite regulation. The expression of key lipid metabolism-related genes was tested via qRT-PCR, and the lipid and fatty acid composition of the longissimus thoracis were determined. Dietary GSPs at different concentrations upregulated lipoprotein lipase (LPL), which is involved in lipolysis, and significantly increased the mRNA expression levels of carnitine palmitoyltransferase-1B (CPT1B) and cluster of differentiation 36 (CD36), implicated in transmembrane transport of fatty acids. Dietary supplementation of GSPs at 200 or 250 mg/kg markedly reduced total cholesterol and triglyceride content in longissimus thoracis. Dietary GSPs significantly decreased the contents of low-density lipoprotein cholesterol and saturated fatty acids, while increasing unsaturated fatty acids. In conclusion, GSPs may regulate lipid metabolism, reducing cholesterol level, and improving fatty acid composition in the longissimus thoracis of growing-finishing pigs. Our findings provide evidence for the beneficial effects of GSPs as pig feed additives for improving lipid composition.
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Affiliation(s)
- Yue Zhang
- College of Animal Science, Shanxi Agricultural University, Taigu 030801, China
| | - Yan Zhai
- College of Animal Science, Shanxi Agricultural University, Taigu 030801, China
| | - Xinxin Wei
- College of Animal Science, Shanxi Agricultural University, Taigu 030801, China
| | - Xu Yang
- College of Animal Science, Shanxi Agricultural University, Taigu 030801, China
| | - Chao Deng
- College of Animal Science, Shanxi Agricultural University, Taigu 030801, China
| | - Qinghong Li
- College of Animal Science, Shanxi Agricultural University, Taigu 030801, China
| | - Weiwei Wang
- College of Animal Science, Shanxi Agricultural University, Taigu 030801, China
| | - Ruirong Hao
- College of Animal Science, Shanxi Agricultural University, Taigu 030801, China; Key Laboratory of Farm Animal Genetic Resources Exploration and Breeding of Shanxi Province, Taigu 030801, China.
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3
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Tveter KM, Mezhibovsky E, Wu Y, Roopchand DE. Bile acid metabolism and signaling: Emerging pharmacological targets of dietary polyphenols. Pharmacol Ther 2023; 248:108457. [PMID: 37268113 PMCID: PMC10528343 DOI: 10.1016/j.pharmthera.2023.108457] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 04/03/2023] [Accepted: 05/22/2023] [Indexed: 06/04/2023]
Abstract
Beyond their role as emulsifiers of lipophilic compounds, bile acids (BAs) are signaling endocrine molecules that show differential affinity and specificity for a variety of canonical and non-canonical BA receptors. Primary BAs (PBAs) are synthesized in the liver while secondary BAs (SBAs) are gut microbial metabolites of PBA species. PBAs and SBAs signal to BA receptors that regulate downstream pathways of inflammation and energy metabolism. Dysregulation of BA metabolism or signaling has emerged as a feature of chronic disease. Dietary polyphenols are non-nutritive plant-derived compounds associated with decreased risk of metabolic syndrome, type-2 diabetes, hepatobiliary and cardiovascular disease. Evidence suggests that the health promoting effects of dietary polyphenols are linked to their ability to alter the gut microbial community, the BA pool, and BA signaling. In this review we provide an overview of BA metabolism and summarize studies that link the cardiometabolic improvements of dietary polyphenols to their modulation of BA metabolism and signaling pathways, and the gut microbiota. Finally, we discuss approaches and challenges in deciphering cause-effect relationships between dietary polyphenols, BAs, and gut microbes.
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Affiliation(s)
- Kevin M Tveter
- Rutgers, The State University of New Jersey, Department of Food Science, Institute for Food Nutrition and Health [Center for Microbiome, Nutrition and Health & Rutgers Center for Lipid Research], 61 Dudley Road, New Brunswick, NJ 08901, USA
| | - Esther Mezhibovsky
- Rutgers, The State University of New Jersey, Department of Food Science, Institute for Food Nutrition and Health [Center for Microbiome, Nutrition and Health & Rutgers Center for Lipid Research], 61 Dudley Road, New Brunswick, NJ 08901, USA
| | - Yue Wu
- Rutgers, The State University of New Jersey, Department of Food Science, Institute for Food Nutrition and Health [Center for Microbiome, Nutrition and Health & Rutgers Center for Lipid Research], 61 Dudley Road, New Brunswick, NJ 08901, USA
| | - Diana E Roopchand
- Rutgers, The State University of New Jersey, Department of Food Science, Institute for Food Nutrition and Health [Center for Microbiome, Nutrition and Health & Rutgers Center for Lipid Research], 61 Dudley Road, New Brunswick, NJ 08901, USA.
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4
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Jia X, Dong L, Wen Y, Huang F, Chi J, Zhang R. Discovery of possible hepatoprotective components from lychee pulp phenolic extract by online knockout methods. FOOD BIOSCI 2022. [DOI: 10.1016/j.fbio.2022.102053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
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5
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Torres‐Fuentes C, Suárez M, Aragonès G, Mulero M, Ávila‐Román J, Arola‐Arnal A, Salvadó MJ, Arola L, Bravo FI, Muguerza B. Cardioprotective Properties of Phenolic Compounds: A Role for Biological Rhythms. Mol Nutr Food Res 2022; 66:e2100990. [PMID: 35279936 PMCID: PMC9786928 DOI: 10.1002/mnfr.202100990] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 01/25/2022] [Indexed: 12/30/2022]
Abstract
Cardiovascular diseases (CVD) are the leading cause of deaths worldwide and their prevalence is continuously increasing. Available treatments may present several side effects and therefore the development of new safer therapeutics is of interest. Phenolic compounds have shown several cardioprotective properties helpful in reducing different CVD risk factors such as inflammation, elevated blood pressure, hyperlipidemia, or endothelial dysfunction. These factors are significantly influenced by biological rhythms which are in fact emerging as key modulators of important metabolic and physiological processes. Thus, increased events of CVD have been observed under circadian rhythm disruption or in winter versus other seasons. These rhythms can also affect the functionality of phenolic compounds. Indeed, different effects have been observed depending on the administration time or under different photoperiods. Therefore, in this review the focus will be on the potential of phenolic compounds as therapeutics to prevent CVD via biological rhythm modulation.
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Affiliation(s)
- Cristina Torres‐Fuentes
- Nutrigenomics Research GroupDepartament de Bioquímica i BiotecnologiaUniversitat Rovira i VirgiliTarragona43007Spain
| | - Manuel Suárez
- Nutrigenomics Research GroupDepartament de Bioquímica i BiotecnologiaUniversitat Rovira i VirgiliTarragona43007Spain
| | - Gerard Aragonès
- Nutrigenomics Research GroupDepartament de Bioquímica i BiotecnologiaUniversitat Rovira i VirgiliTarragona43007Spain
| | - Miquel Mulero
- Nutrigenomics Research GroupDepartament de Bioquímica i BiotecnologiaUniversitat Rovira i VirgiliTarragona43007Spain
| | - Javier Ávila‐Román
- Nutrigenomics Research GroupDepartament de Bioquímica i BiotecnologiaUniversitat Rovira i VirgiliTarragona43007Spain
| | - Anna Arola‐Arnal
- Nutrigenomics Research GroupDepartament de Bioquímica i BiotecnologiaUniversitat Rovira i VirgiliTarragona43007Spain
| | - Maria Josepa Salvadó
- Nutrigenomics Research GroupDepartament de Bioquímica i BiotecnologiaUniversitat Rovira i VirgiliTarragona43007Spain
| | - Lluís Arola
- Nutrigenomics Research GroupDepartament de Bioquímica i BiotecnologiaUniversitat Rovira i VirgiliTarragona43007Spain
| | - Francisca Isabel Bravo
- Nutrigenomics Research GroupDepartament de Bioquímica i BiotecnologiaUniversitat Rovira i VirgiliTarragona43007Spain
| | - Begoña Muguerza
- Nutrigenomics Research GroupDepartament de Bioquímica i BiotecnologiaUniversitat Rovira i VirgiliTarragona43007Spain
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Li Y, Zhu L, Guo C, Xue M, Xia F, Wang Y, Jia D, Li L, Gao Y, Shi Y, He Y, Yuan C. Dietary Intake of Hydrolyzable Tannins and Condensed Tannins to Regulate Lipid Metabolism. Mini Rev Med Chem 2021; 22:1789-1802. [PMID: 34967286 DOI: 10.2174/1389557522666211229112223] [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: 06/10/2021] [Revised: 09/23/2021] [Accepted: 10/03/2021] [Indexed: 11/22/2022]
Abstract
Lipid metabolism disorder is a multifactor issue, which contributes to several serious health consequences, such as obesity, hyperlipidemia, atherosclerosis diabetes, non-alcoholic fatty liver etc. Tannins, applied as natural derived plant, are commonly used in the study of lipid metabolism disease with excellent safety and effectiveness, while producing less toxic and side effects. Meanwhile, recognition of the significance of dietary tannins in lipid metabolism disease prevention has increased. As suggested by existing evidence, dietary tannins can reduce lipid accumulation, block adipocyte differentiation, enhance antioxidant capacity, increase the content of short-chain fatty acids, and lower blood lipid levels, thus alleviating lipid metabolism disorder. This study is purposed to sum up and analyze plenty of documents on tannins, so as to provide the information required to assess the lipid metabolism of tannins.
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Affiliation(s)
- Yuanyang Li
- College of Medical Science, China Three Gorges University, Yichang, China
| | - Leiqi Zhu
- College of Medical Science, China Three Gorges University, Yichang, China
| | - Chong Guo
- College of Medical Science, China Three Gorges University, Yichang, China
| | - Mengzhen Xue
- College of Medical Science, China Three Gorges University, Yichang, China
| | - Fangqi Xia
- College of Medical Science, China Three Gorges University, Yichang, China
| | - Yaqi Wang
- College of Medical Science, China Three Gorges University, Yichang, China
| | - Dengke Jia
- College of Medical Science, China Three Gorges University, Yichang, China
| | - Luoying Li
- College of Medical Science, China Three Gorges University, Yichang, China
| | - Yan Gao
- College of Medical Science, China Three Gorges University, Yichang, China
| | - Yue Shi
- College of Medical Science, China Three Gorges University, Yichang, China
| | - Yuming He
- College of Medical Science, China Three Gorges University, Yichang, China
- Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges, Yichang, China
| | - Chengfu Yuan
- College of Medical Science, China Three Gorges University, Yichang, China
- Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges, Yichang, China
- Hubei Key Laboratory of Tumour Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China
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7
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Proanthocyanidins and Where to Find Them: A Meta-Analytic Approach to Investigate Their Chemistry, Biosynthesis, Distribution, and Effect on Human Health. Antioxidants (Basel) 2021; 10:antiox10081229. [PMID: 34439477 PMCID: PMC8389005 DOI: 10.3390/antiox10081229] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 07/26/2021] [Accepted: 07/27/2021] [Indexed: 12/22/2022] Open
Abstract
Proanthocyanidins (PACs) are a class of polyphenolic compounds that are attracting considerable interest in the nutraceutical field due to their potential health benefits. However, knowledge about the chemistry, biosynthesis, and distribution of PACs is limited. This review summarizes the main chemical characteristics and biosynthetic pathways and the main analytical methods aimed at their identification and quantification in raw plant matrices. Furthermore, meta-analytic approaches were used to identify the main plant sources in which PACs were contained and to investigate their potential effect on human health. In particular, a cluster analysis identified PACs in 35 different plant families and 60 different plant parts normally consumed in the human diet. On the other hand, a literature search, coupled with forest plot analyses, highlighted how PACs can be actively involved in both local and systemic effects. Finally, the potential mechanisms of action through which PACs may impact human health were investigated, focusing on their systemic hypoglycemic and lipid-lowering effects and their local anti-inflammatory actions on the intestinal epithelium. Overall, this review may be considered a complete report in which chemical, biosynthetic, ecological, and pharmacological aspects of PACs are discussed.
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8
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Monfoulet LE, Ruskovska T, Ajdžanović V, Havlik J, Vauzour D, Bayram B, Krga I, Corral-Jara KF, Kistanova E, Abadjieva D, Massaro M, Scoditti E, Deligiannidou E, Kontogiorgis C, Arola-Arnal A, van Schothorst EM, Morand C, Milenkovic D. Molecular Determinants of the Cardiometabolic Improvements of Dietary Flavanols Identified by an Integrative Analysis of Nutrigenomic Data from a Systematic Review of Animal Studies. Mol Nutr Food Res 2021; 65:e2100227. [PMID: 34048642 DOI: 10.1002/mnfr.202100227] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 05/21/2021] [Indexed: 12/11/2022]
Abstract
SCOPE Flavanols are important polyphenols of the human diet with extensive demonstrations of their beneficial effects on cardiometabolic health. They contribute to preserve health acting on a large range of cellular processes. The underlying mechanisms of action of flavanols are not fully understood but involve a nutrigenomic regulation. METHODS AND RESULTS To further capture how the intake of dietary flavanols results in the modulation of gene expression, nutrigenomics data in response to dietary flavanols obtained from animal models of cardiometabolic diseases have been collected and submitted to a bioinformatics analysis. This systematic analysis shows that dietary flavanols modulate a large range of genes mainly involved in endocrine function, fatty acid metabolism, and inflammation. Several regulators of the gene expression have been predicted and include transcription factors, miRNAs and epigenetic factors. CONCLUSION This review highlights the complex and multilevel action of dietary flavanols contributing to their strong potential to preserve cardiometabolic health. The identification of the potential molecular mediators and of the flavanol metabolites driving the nutrigenomic response in the target organs is still a pending question which the answer will contribute to optimize the beneficial health effects of dietary bioactives.
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Affiliation(s)
| | - Tatjana Ruskovska
- Faculty of Medical Sciences, Goce Delcev University, Stip, North Macedonia
| | - Vladimir Ajdžanović
- Department of Cytology, Institute for Biological Research "Siniša Stanković,", National Institute of Republic of Serbia, University of Belgrade, 142 Despot Stefan Blvd., Belgrade, Serbia
| | - Jaroslav Havlik
- Department of Food Science, Czech University of Life Sciences Prague, Prague 6, Suchdol, Czech Republic
| | - David Vauzour
- Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK
| | - Banu Bayram
- Department of Nutrition and Dietetics, University of Health Sciences, Istanbul, Turkey
| | - Irena Krga
- Université Clermont Auvergne, INRAE, UNH, Clermont-Ferrand, F-63000, France.,Centre of Excellence in Nutrition and Metabolism Research, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | | | - Elena Kistanova
- Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Desislava Abadjieva
- Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Marika Massaro
- National Research Council (CNR) Institute of Clinical Physiology, Lecce, Italy
| | - Egeria Scoditti
- National Research Council (CNR) Institute of Clinical Physiology, Lecce, Italy
| | - Eirini Deligiannidou
- Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, Alexandroupolis, 68100, Greece
| | - Christos Kontogiorgis
- Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, Alexandroupolis, 68100, Greece
| | - Anna Arola-Arnal
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Nutrigenomics Research Group, Tarragona, 43007, Spain
| | | | - Christine Morand
- Université Clermont Auvergne, INRAE, UNH, Clermont-Ferrand, F-63000, France
| | - Dragan Milenkovic
- Université Clermont Auvergne, INRAE, UNH, Clermont-Ferrand, F-63000, France.,Department of Internal Medicine, Division of Cardiovascular Medicine, School of Medicine, University of California Davis, Davis, California, 95616, USA
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9
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Ávila-Román J, Soliz-Rueda JR, Bravo FI, Aragonès G, Suárez M, Arola-Arnal A, Mulero M, Salvadó MJ, Arola L, Torres-Fuentes C, Muguerza B. Phenolic compounds and biological rhythms: Who takes the lead? Trends Food Sci Technol 2021. [DOI: 10.1016/j.tifs.2021.04.050] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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10
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ISHIMOTO EY, VICENTE SJV, CRUZ RJ, TORRES EAFDS. Hypolipidemic and antioxidant effects of grape processing by-products in high-fat/cholesterol diet-induced hyperlipidemic hamsters. FOOD SCIENCE AND TECHNOLOGY 2020. [DOI: 10.1590/fst.32619] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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11
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Barbe A, Mellouk N, Ramé C, Grandhaye J, Staub C, Venturi E, Cirot M, Petit A, Anger K, Chahnamian M, Ganier P, Callut O, Cailleau-Audouin E, Metayer-Coustard S, Riva A, Froment P, Dupont J. A grape seed extract maternal dietary supplementation in reproductive hens reduces oxidative stress associated to modulation of plasma and tissue adipokines expression and improves viability of offsprings. PLoS One 2020; 15:e0231131. [PMID: 32282838 PMCID: PMC7153862 DOI: 10.1371/journal.pone.0231131] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Accepted: 03/17/2020] [Indexed: 01/06/2023] Open
Abstract
In reproductive hens, a feed restriction is an usual practice to improve metabolic and reproductive disorders. However, it acts a stressor on the animal. In mammals, grape seed extracts (GSE) reduces oxidative stress. However, their effect on endocrine and tissue response need to be deepened in reproductive hens. Here, we evaluated the effects of time and level of GSE dietary supplementation on growth performance, viability, oxidative stress and metabolic parameters in plasma and metabolic tissues in reproductive hens and their offsprings. We designed an in vivo trial using 4 groups of feed restricted hens: A (control), B and C (supplemented with 0.5% and 1% of the total diet composition in GSE since week 4, respectively) and D (supplemented with 1% of GSE since the hatch). In hens from hatch to week 40, GSE supplementation did not affect food intake and fattening whatever the time and dose of supplementation. Body weight was significantly reduced in D group as compared to control. In all hen groups, GSE supplementation decreased plasma oxidative stress index associated to a decrease in the mRNA expression of the NOX4 and 5 oxidant genes in liver and muscle and an increase in SOD mRNA expression. This was also associated to decreased plasma chemerin and increased plasma adiponectin and visfatin levels. Interestingly, maternal GSE supplementation increased the live body weight and viability of chicks at hatching and 10 days of age. This was associated to a decrease in plasma and liver oxidative stress parameters. Taken together, GSE maternal dietary supplementation reduces plasma and tissue oxidative stress associated to modulation of adipokines without affecting fattening in reproductive hens. A 1% GSE maternal dietary supplementation increased offspring viability and reduced oxidative stress suggesting a beneficial transgenerational effect and a potential use to improve the quality of the progeny in reproductive hens.
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Affiliation(s)
- Alix Barbe
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France.,CNRS UMR7247 Physiologie de la Reproduction et des Comportements, Nouzilly, France.,Université François Rabelais de Tours, Tours, France.,IFCE, Nouzilly, France
| | - Namya Mellouk
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France.,CNRS UMR7247 Physiologie de la Reproduction et des Comportements, Nouzilly, France.,Université François Rabelais de Tours, Tours, France.,IFCE, Nouzilly, France
| | - Christelle Ramé
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France.,CNRS UMR7247 Physiologie de la Reproduction et des Comportements, Nouzilly, France.,Université François Rabelais de Tours, Tours, France.,IFCE, Nouzilly, France
| | - Jérémy Grandhaye
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France.,CNRS UMR7247 Physiologie de la Reproduction et des Comportements, Nouzilly, France.,Université François Rabelais de Tours, Tours, France.,IFCE, Nouzilly, France
| | - Christophe Staub
- INRAE - Unité Expérimentale de Physiologie Animale de l'Orfrasière UEPAO 1297, Nouzilly, France
| | - Eric Venturi
- INRAE - Unité Expérimentale de Physiologie Animale de l'Orfrasière UEPAO 1297, Nouzilly, France
| | - Marine Cirot
- INRAE - Unité Expérimentale de Physiologie Animale de l'Orfrasière UEPAO 1297, Nouzilly, France
| | - Angélique Petit
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France.,CNRS UMR7247 Physiologie de la Reproduction et des Comportements, Nouzilly, France.,Université François Rabelais de Tours, Tours, France.,IFCE, Nouzilly, France
| | - Karine Anger
- INRAE - Unité Expérimentale du Pôle d'Expérimentation Avicole de Tours UEPEAT, 1295, Nouzilly, France
| | - Marine Chahnamian
- INRAE - Unité Expérimentale du Pôle d'Expérimentation Avicole de Tours UEPEAT, 1295, Nouzilly, France
| | - Patrice Ganier
- INRAE - Unité Expérimentale du Pôle d'Expérimentation Avicole de Tours UEPEAT, 1295, Nouzilly, France
| | - Olivier Callut
- INRAE - Unité Expérimentale du Pôle d'Expérimentation Avicole de Tours UEPEAT, 1295, Nouzilly, France
| | | | | | | | - Pascal Froment
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France.,CNRS UMR7247 Physiologie de la Reproduction et des Comportements, Nouzilly, France.,Université François Rabelais de Tours, Tours, France.,IFCE, Nouzilly, France
| | - Joëlle Dupont
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France.,CNRS UMR7247 Physiologie de la Reproduction et des Comportements, Nouzilly, France.,Université François Rabelais de Tours, Tours, France.,IFCE, Nouzilly, France
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12
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Castro MC, Villagarcía H, Nazar A, Arbeláez LG, Massa ML, Del Zotto H, Ríos JL, Schinella GR, Francini F. Cacao extract enriched in polyphenols prevents endocrine-metabolic disturbances in a rat model of prediabetes triggered by a sucrose rich diet. JOURNAL OF ETHNOPHARMACOLOGY 2020; 247:112263. [PMID: 31580944 DOI: 10.1016/j.jep.2019.112263] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 09/23/2019] [Accepted: 09/29/2019] [Indexed: 06/10/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Cocoa extracts rich in polyphenols are used as potential agent for treating diabetes. Cocoa polyphenols have been proved to ameliorate important hallmarks of type-2 diabetes (T2D). They can regulate glucose levels by increasing insulin secretion, promoting β-cell proliferation and a reduction of insulin resistance. In addition, epidemiological evidence indicates that consumption of flavonoid decreases the incidence of T2D. AIM OF THE STUDY T2D is preceded by a prediabetic state in which the endocrine-metabolic changes described in T2D are already present. Since epidemiological evidence indicates that consumption of flavonoid decreases its incidence, we evaluated possible preventive effects of polyphenol-enriched cocoa extract on a model of prediabetes induced by sucrose. MATERIALS AND METHODS We determined circulating parameters and insulin sensitivity indexes, liver protein carbonyl groups and reduced glutathione, liver mRNA expression levels of lipogenic enzymes, expression of different pro-inflammatory mediators, fructokinase activity and liver glycogen content. For that, radioimmunoassay, real-time polymerase chain reaction, Western blot, spectrophotometry, and immunohistochemistry were used. RESULTS We demonstrated that sucrose administration triggered hypertriglyceridemia, insulin-resistance, and liver increased oxidative stress and inflammation markers compared to control rats. Additionally, we found an increase in glycogen deposit, fructokinase activity, and lipogenic genes expression (SREBP-1c, FAS and GPAT) together with a decrease in P-Akt and P-eNOS protein content (P < 0.05). Sucrose-induced insulin resistance, hepatic carbohydrate and lipid dysmetabolism, oxidative stress, and inflammation were effectively disrupted by polyphenol-enriched cocoa extract (PECE) co-administration (P < 0.05). CONCLUSION Dietary administration of cocoa flavanols may be an effective and complementary tool for preventing or reverting T2D at an early stage of its development (prediabetes).
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Affiliation(s)
- María Cecilia Castro
- CENEXA (Centro de Endocrinología Experimental y Aplicada) (UNLP-CONICET La Plata-FCM, CEAS-CICPBA), La Plata, Argentina
| | - Hernán Villagarcía
- CENEXA (Centro de Endocrinología Experimental y Aplicada) (UNLP-CONICET La Plata-FCM, CEAS-CICPBA), La Plata, Argentina
| | - Ada Nazar
- CENEXA (Centro de Endocrinología Experimental y Aplicada) (UNLP-CONICET La Plata-FCM, CEAS-CICPBA), La Plata, Argentina
| | - Luisa González Arbeláez
- CIC (Centro de Investigaciones Cardiovasculares) (UNLP-CONICET La Plata-FCM), La Plata, Argentina
| | - María Laura Massa
- CENEXA (Centro de Endocrinología Experimental y Aplicada) (UNLP-CONICET La Plata-FCM, CEAS-CICPBA), La Plata, Argentina
| | - Héctor Del Zotto
- CENEXA (Centro de Endocrinología Experimental y Aplicada) (UNLP-CONICET La Plata-FCM, CEAS-CICPBA), La Plata, Argentina
| | - José Luis Ríos
- Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot, Spain
| | - Guillermo R Schinella
- Cátedra Farmacología Básica, Facultad de Ciencias Médicas UNLP and CICPBA, La Plata, Argentina
| | - Flavio Francini
- CENEXA (Centro de Endocrinología Experimental y Aplicada) (UNLP-CONICET La Plata-FCM, CEAS-CICPBA), La Plata, Argentina.
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Ginés I, Gil-Cardoso K, Serrano J, Casanova-Marti À, Lobato M, Terra X, Blay MT, Ardévol A, Pinent M. Proanthocyanidins Limit Adipose Accrual Induced by a Cafeteria Diet, Several Weeks after the End of the Treatment. Genes (Basel) 2019; 10:genes10080598. [PMID: 31398921 PMCID: PMC6723337 DOI: 10.3390/genes10080598] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 07/19/2019] [Accepted: 08/05/2019] [Indexed: 11/25/2022] Open
Abstract
A dose of proanthocyanidins with satiating properties proved to be able to limit body weight increase several weeks after administration under exposure to a cafeteria diet. Here we describe some of the molecular targets and the duration of the effects. We treated rats with 500 mg grape seed proanthocyanidin extract (GSPE)/kg BW for ten days. Seven or seventeen weeks after the last GSPE dose, while animals were on a cafeteria diet, we used reverse transcriptase-polymerase chain reaction (RT-PCR) to measure the mRNA of the key energy metabolism enzymes from the liver, adipose depots and muscle. We found that a reduction in the expression of adipose Lpl might explain the lower amount of adipose tissue in rats seven weeks after the last GSPE dose. The liver showed increased expression of Cpt1a and Hmgs2 together with a reduction in Fasn and Dgat2. In addition, muscle showed a higher fatty oxidation (Oxct1 and Cpt1b mRNA). However, after seventeen weeks, there was a completely different gene expression pattern. At the conclusion of the study, seven weeks after the last GSPE administration there was a limitation in adipose accrual that might be mediated by an inhibition of the gene expression of the adipose tissue Lpl. Concomitantly there was an increase in fatty acid oxidation in liver and muscle.
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Affiliation(s)
- Iris Ginés
- MoBioFood Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, c/Marcel·lí Domingo n°1, 43007 Tarragona, Spain
| | - Katherine Gil-Cardoso
- MoBioFood Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, c/Marcel·lí Domingo n°1, 43007 Tarragona, Spain
| | - Joan Serrano
- MoBioFood Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, c/Marcel·lí Domingo n°1, 43007 Tarragona, Spain
| | - Àngela Casanova-Marti
- MoBioFood Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, c/Marcel·lí Domingo n°1, 43007 Tarragona, Spain
| | - Maria Lobato
- MoBioFood Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, c/Marcel·lí Domingo n°1, 43007 Tarragona, Spain
| | - Ximena Terra
- MoBioFood Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, c/Marcel·lí Domingo n°1, 43007 Tarragona, Spain
| | - M Teresa Blay
- MoBioFood Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, c/Marcel·lí Domingo n°1, 43007 Tarragona, Spain
| | - Anna Ardévol
- MoBioFood Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, c/Marcel·lí Domingo n°1, 43007 Tarragona, Spain.
| | - Montserrat Pinent
- MoBioFood Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, c/Marcel·lí Domingo n°1, 43007 Tarragona, Spain
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Nie Y, Stürzenbaum SR. Proanthocyanidins of Natural Origin: Molecular Mechanisms and Implications for Lipid Disorder and Aging-Associated Diseases. Adv Nutr 2019; 10:464-478. [PMID: 30926997 PMCID: PMC6520035 DOI: 10.1093/advances/nmy118] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 07/06/2018] [Accepted: 11/27/2018] [Indexed: 12/27/2022] Open
Abstract
Proanthocyanidins are phytonutrients formed by oligomerization or polymerization of subunits catechin, epicatechin, and their gallic acid esters. Proanthocyanidins are a component of many plants and thus form an integral part of the human diet. Oligomeric proanthocyanidins are currently marketed as medicinal products that target vascular disorders and chronic pathological conditions, many of which are age-associated. Proanthocyanidins are also characterized by their effects on energy homeostasis. Not dissimilar to their chemically synthesized counterparts, naturally extracted proanthocyanidins act via inhibition of lipases, stimulation of energy expenditure, or suppression of appetite. Here we review the current knowledge-base and highlight challenges and future impacts regarding involvement of proanthocyanidins in global lipid metabolism, with a focus on the molecular mechanisms and pathological conditions that progress with aging.
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Affiliation(s)
- Yu Nie
- Department of Analytical, Environmental & Forensic Sciences, School of Population Health & Environmental Sciences, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom
| | - Stephen R Stürzenbaum
- Department of Analytical, Environmental & Forensic Sciences, School of Population Health & Environmental Sciences, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom
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15
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Li X, Chen Y, Li S, Chen M, Xiao J, Xie B, Sun Z. Oligomer Procyanidins from Lotus Seedpod Regulate Lipid Homeostasis Partially by Modifying Fat Emulsification and Digestion. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:4524-4534. [PMID: 30945544 DOI: 10.1021/acs.jafc.9b01469] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Dietary polyphenols have shown hypolipidemic effects by reducing triglyceride absorption. The mechanisms may involve modifying fat emulsion during digestion in the gastrointestinal tract and suppressing lipase during hydrolysis in the small intestine. In an in vivo study, lotus seedpod oligomeric procyanidin (LSOPC) decreased total serum triglyceride and total cholesterol and elevated the high-density lipoprotein level in the hyperlipidemic rat model. In addition, LSOPC suppressed de novo lipogenesis-related gene expressions. In an in vitro study, the LSOPC-enriched emulsion decreased the mean droplet size from 0.36 to 0.33 μm and increased the viscosity of the emulsion. Moreover, the LSOPC-enriched emulsion improved the antioxidant properties. A digestion model was developed and showed that the particle size of the LSOPC-enriched emulsion increased in the oral cavity. However, an increase and then a significant drop of the particle size was measured in the stomach and small intestine. The free fatty acid release rate was decreased in the LSOPC-enriched emulsion partly ascribed to the inhibition of lipase by LSOPC.
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Affiliation(s)
| | | | - Shuyi Li
- College of Food Science and Engineering , Wuhan Polytechnic University , Wuhan , Hubei 430023 , People's Republic of China
| | | | - Juan Xiao
- College of Food Science and Technology , Hainan University , Haikou , Hainan 570228 , People's Republic of China
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16
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Xing YW, Lei GT, Wu QH, Jiang Y, Huang MX. Procyanidin B2 protects against diet-induced obesity and non-alcoholic fatty liver disease via the modulation of the gut microbiota in rabbits. World J Gastroenterol 2019; 25:955-966. [PMID: 30833801 PMCID: PMC6397725 DOI: 10.3748/wjg.v25.i8.955] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Revised: 01/25/2019] [Accepted: 01/28/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Procyanidins have beneficial effects on metabolic syndrome and antimicrobial activity, but the mechanisms underlying these effects are unclear.
AIM To investigate the effects of procyanidin B2 (PB2) on non-alcoholic fatty liver disease and to explore the possible mechanism.
METHODS Thirty male New Zealand white rabbits were randomized into three groups. All of them were fed either a high-fat-cholesterol diet (HCD) or chow diet. HCD-fed rabbits were treated with vehicle or PB2 daily for 12 wk. Body weight and food intake were evaluated once a week. Serum biomarkers, such as total cholesterols, triglycerides, and aspartate transaminase, were detected. All rabbits were sacrificed and histological parameters of liver were assessed by hematoxylin and eosin-stained sections. Moreover, several lipogenic genes and gut microbiota (by 16S rRNA sequencing) were investigated to explore the possible mechanism.
RESULTS The HCD group had higher body weight, liver index, serum lipid profile, insulin resistance, serum glucose, and hepatic steatosis compared to the CHOW group. PB2 treatment prevented HCD-induced increases in body weight and hypertriglyceridemia in association with triglyceride accumulation in the liver. PB2 also ameliorated low-grade inflammation, which was reflected by serum lipopolysaccharides and improved insulin resistance. In rabbit liver, PB2 prevented the upregulation of steroid response element binding protein 1c and fatty acid synthase and the downregulation of carnitine palmitoyltransferase, compared to the HCD group. Moreover, HCD led to a decrease of Bacteroidetes in gut microbiota. PB2 significantly improved the proportions of Bacteroidetes at the phylum level and Akkermansia at the genus level.
CONCLUSION Our results indicate the possible mechanism of PB2 to improve HCD-induced features of metabolic syndrome and provide a new dietary supplement.
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Affiliation(s)
- Ya-Wei Xing
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Guang-Tao Lei
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Qing-Hua Wu
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Yu Jiang
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Man-Xiang Huang
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
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17
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Wei S, Zheng Y, Zhang M, Zheng H, Yan P. Grape seed procyanidin extract inhibits adipogenesis and stimulates lipolysis of porcine adipocytes in vitro. J Anim Sci 2018; 96:2753-2762. [PMID: 29701782 DOI: 10.1093/jas/sky158] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Accepted: 04/24/2018] [Indexed: 12/17/2022] Open
Abstract
The objective of this article was to evaluate in vitro effect of grape seed procyanidin extract (GSPE) on differentiation, proliferation, and lipolysis of porcine adipocytes, providing a molecular basis for the use of GSPE in pig fat regulation. Primary preadipocytes isolated from subcutaneous adipose tissue of pigs were used as the in vitro cell model. Treatment of GSPE repressed preadipocyte differentiation, as evidenced by reduced lipid accumulation, decreased mRNA expressions of peroxisome proliferator-activated receptor gamma (PPARγ) and fatty acid-binding protein 4 (FABP4), as well as enhanced expressions of preadipocyte factor-1. Activity of glycerol-3-phosphate dehydrogenase (GPDH), one of the most important enzymes in the pathway for triacylglycerol biosynthesis, was also decreased. Furthermore, GSPE could suppress preadipocyte proliferation by inducing G0/G1 cell cycle arrest and cell apoptosis. In porcine mature adipocytes, treatment with GSPE attenuated lipid content and GPDH activity, and the release of both free fatty acid and glycerol were enhanced; mRNA expressions of key lipolytic transcription factors, including hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL), were elevated in GSPE-treated adipocytes. In summary, our results suggest GSPE inhibits porcine preadipocyte differentiation and proliferation and stimulates lipolysis of mature adipocytes, thus providing novel insights for further exploring the use of GSPE as a fat accumulation inhibitor.
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Affiliation(s)
- Shengjuan Wei
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, P R China
| | - Yueying Zheng
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, P R China
| | - Mengmeng Zhang
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, P R China
| | - Hao Zheng
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, P R China
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18
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Alfaro-Viquez E, Roling BF, Krueger CG, Rainey CJ, Reed JD, Ricketts ML. An extract from date palm fruit (Phoenix dactylifera) acts as a co-agonist ligand for the nuclear receptor FXR and differentially modulates FXR target-gene expression in vitro. PLoS One 2018; 13:e0190210. [PMID: 29293579 PMCID: PMC5749773 DOI: 10.1371/journal.pone.0190210] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Accepted: 12/11/2017] [Indexed: 02/07/2023] Open
Abstract
Date palm fruit (Phoenix dactylifera) consumption reduces serum triglyceride levels in human subjects. The objective of this study was to prepare an extract from dates and determine whether it acts as a ligand for the farnesoid x receptor (FXR), a nuclear receptor important for maintaining triglyceride and cholesterol homeostasis. Freeze-dried extracts were isolated from California-grown dates (Deglet Noor and Medjool) from the 2014 and 2015 harvests, by means of liquid extraction and solid phase separation. Each date palm extract (DPE) was characterized via HPLC and MALDI-TOF mass spectrometry, and the procyanidin content was qualitatively determined. Extracts were tested to determine their ability to modulate nuclear receptor-mediated transactivation using transient transfection. The effect of DPE on FXR-target genes regulating bile acid absorption and transport was then assessed in vitro, in Caco-2 cells. Characterization reveals that DPE is a rich source of polyphenols including hydroxycinnamic acids, proanthocyanidins, and lipohilic polyphenols, and comprises 13% proanthocyanidins. Transactivation results show that DPE acts as a co-agonist ligand for both mouse and human FXR, wherein it activates bile acid-bound FXR greater than that seen with bile acid alone. Additionally, DPE alone activated a peroxisome proliferator activated receptor alpha (PPARα) chimera in a dose-dependent manner. Consistent with DPE as a co-agonist ligand for FXR, studies in Caco-2 cells reveal that co-incubation with bile acid, dose-dependently enhances the expression of fibroblast growth factor 19 (FGF19), compared to treatment with bile acid alone. In contrast, DPE inhibited bile acid-induced expression of ileal bile acid binding protein (IBABP). Our results demonstrate that DPE acts as a potent co-agonist ligand for FXR, and that it differentially regulates FXR-target gene expression in vitro in human intestinal cells. This study provides novel insight into a potential mechanism by which dates may exert a hypotriglyceridemic effect via FXR and modulation of bile acid homeostasis.
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Affiliation(s)
- Emilia Alfaro-Viquez
- Reed Research Group, Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, United States of America
| | - Brent F. Roling
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada, Reno, Reno, NV, United States of America
| | - Christian G. Krueger
- Reed Research Group, Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, United States of America
- Complete Phytochemical Solutions, Cambridge, WI, United States of America
| | - Charlene J. Rainey
- Date Research Institute, San Juan Capistrano, CA, United States of America
| | - Jess D. Reed
- Reed Research Group, Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, United States of America
- Complete Phytochemical Solutions, Cambridge, WI, United States of America
| | - Marie-Louise Ricketts
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada, Reno, Reno, NV, United States of America
- * E-mail:
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19
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Rong S, Zhao S, Kai X, Zhang L, Zhao Y, Xiao X, Bao W, Liu L. Procyanidins extracted from the litchi pericarp attenuate atherosclerosis and hyperlipidemia associated with consumption of a high fat diet in apolipoprotein-E knockout mice. Biomed Pharmacother 2017; 97:1639-1644. [PMID: 29793326 DOI: 10.1016/j.biopha.2017.10.139] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2017] [Revised: 10/15/2017] [Accepted: 10/24/2017] [Indexed: 12/13/2022] Open
Abstract
The beneficial effects of red wine against cardiovascular disease are associated with the abundant antioxidant polyphenols such as procyanidins. Recently, procyanidins extracted from the litchi pericarp (LPPC), a new source of procyanidins showed strong antioxidant activities in vitro, have been isolated and identified in our laboratory. The aim of present study was to investigate the anti-atherosclerotic effects of LPPC on atherosclerosis and hyperlipidemia in apolipoprotein E knockout (ApoE KO) mice fed a high fat diet (HFD, 21% fat, 0.15% cholesterol) for 24 weeks. The results showed that LPPC intervention alleviated atherosclerosis, fat accumulation and hyperlipidemia in ApoE KO mice. Furthermore, real-time RT-PCR results showed that LPPC can regulate several key genes involved in hepatic lipid homeostasis, such as increasing mRNA levels of farnesoid X receptor (FXR) and small heterodimer partner (SHP) which emerge as key regulators of lipid homeostasis at the transcriptional level, decreasing mRNA levels of 3-hydroxy-3-Methylglutaryl (HMG)-CoA reductase which mediates cholestrol biosynthesis, and up-regulating the mRNA expressions of ATP-binding cassette transporter-1 (ABCA1) which modulates cholesterol efflux. Thus, these results elucidated that LPPC could alleviate the lipid disorder especially hypercholesteromia and ameliorate atherosclerosis in ApoE-KO mice fed a WTD via regulating gene expression involved in hepatic lipid homeostasis effectively.
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Affiliation(s)
- Shuang Rong
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Nutrition and Food Hygiene, School of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, China; Institute of Nutrition and Chronic Diseases, Wuhan University of Science & Technology, Wuhan, China
| | - Siqi Zhao
- Department of Nutrition and Food Hygiene, School of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, China; Institute of Nutrition and Chronic Diseases, Wuhan University of Science & Technology, Wuhan, China
| | - Xu Kai
- Department of Nutrition and Food Hygiene, School of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, China; Institute of Nutrition and Chronic Diseases, Wuhan University of Science & Technology, Wuhan, China
| | - Li Zhang
- Hubei province hospitals of Chinese and Western medicine, Wuhan, 430015, China
| | - Yanting Zhao
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiao Xiao
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Bao
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liegang Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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20
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Nie Y, Littleton B, Kavanagh T, Abbate V, Bansal SS, Richards D, Hylands P, Stürzenbaum SR. Proanthocyanidin trimer gallate modulates lipid deposition and fatty acid desaturation in
Caenorhabditis elegans. FASEB J 2017; 31:4891-4902. [DOI: 10.1096/fj.201700438r] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Accepted: 07/05/2017] [Indexed: 12/14/2022]
Affiliation(s)
- Yu Nie
- Analytical and Environmental Sciences DivisionFaculty of Life Sciences and Medicine
| | - Brad Littleton
- Department of PhysicsFaculty of Natural and Mathematical SciencesKing’s College LondonLondonUnited Kingdom
| | - Thomas Kavanagh
- Department of PhysicsFaculty of Natural and Mathematical SciencesKing’s College LondonLondonUnited Kingdom
| | - Vincenzo Abbate
- Institute of Pharmaceutical ScienceFaculty of Life Sciences and Medicine
| | | | - David Richards
- Department of PhysicsFaculty of Natural and Mathematical SciencesKing’s College LondonLondonUnited Kingdom
| | - Peter Hylands
- Institute of Pharmaceutical ScienceFaculty of Life Sciences and Medicine
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21
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Rodriguez K, Ricketts M. Determination of the Bioactive Components in a Grape Seed Procyanidin Extract Responsible for Enhanced Farnesoid X Receptor Transactivation. FASEB J 2017. [DOI: 10.1096/fasebj.31.1_supplement.135.4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Kelvin Rodriguez
- Agriculture, Nutrition and Veterinary SciencesUniversity of Nevada RenoRenoNV
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22
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Downing LE, Edgar D, Ellison PA, Ricketts ML. Mechanistic insight into nuclear receptor-mediated regulation of bile acid metabolism and lipid homeostasis by grape seed procyanidin extract (GSPE). Cell Biochem Funct 2017; 35:12-32. [DOI: 10.1002/cbf.3247] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2016] [Revised: 12/13/2016] [Accepted: 12/16/2016] [Indexed: 12/18/2022]
Affiliation(s)
- Laura E. Downing
- Department of Agriculture, Nutrition and Veterinary Sciences; University of Nevada Reno; Reno Nevada USA
| | - Daniel Edgar
- Department of Biochemistry and Molecular Biology; University of Nevada Reno; Reno Nevada USA
| | - Patricia A. Ellison
- Department of Biochemistry and Molecular Biology; University of Nevada Reno; Reno Nevada USA
| | - Marie-Louise Ricketts
- Department of Agriculture, Nutrition and Veterinary Sciences; University of Nevada Reno; Reno Nevada USA
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Viecili PRN, da Silva B, Hirsch GE, Porto FG, Parisi MM, Castanho AR, Wender M, Klafke JZ. Triglycerides Revisited to the Serial. Adv Clin Chem 2017; 80:1-44. [PMID: 28431638 DOI: 10.1016/bs.acc.2016.11.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
This review discusses the role of triglycerides (TGs) in the normal cardiovascular system as well as in the development and clinical manifestation of cardiovascular diseases. Regulation of TGs at the enzymatic and genetic level, in addition to their possible relevance as preclinical and clinical biomarkers, is discussed, culminating with a description of available and emerging treatments. Due to the high complexity of the subject and the vast amount of material in the literature, the objective of this review was not to exhaust the subject, but rather to compile the information to facilitate and improve the understanding of those interested in this topic. The main publications on the topic were sought out, especially those from the last 5 years. The data in the literature still give reason to believe that there is room for doubt regarding the use of TG as disease biomarkers; however, there is increasing evidence for the role of hypertriglyceridemia on the atherosclerotic inflammatory process, cardiovascular outcomes, and mortality.
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A-type procyanidins from litchi pericarp ameliorate hyperglycaemia by regulating hepatic and muscle glucose metabolism in streptozotocin (STZ)-induced diabetic mice fed with high fat diet. J Funct Foods 2016. [DOI: 10.1016/j.jff.2016.08.010] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Downing LE, Ferguson BS, Rodriguez K, Ricketts ML. A grape seed procyanidin extract inhibits HDAC activity leading to increased Pparα phosphorylation and target-gene expression. Mol Nutr Food Res 2016; 61. [PMID: 27624175 DOI: 10.1002/mnfr.201600347] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Revised: 08/30/2016] [Accepted: 09/08/2016] [Indexed: 12/13/2022]
Abstract
SCOPE Histone deacetylases (HDACs) have emerged as epigenetic regulators of risk factors associated with the metabolic syndrome (MetS), and certain botanical extracts have proven to be potent HDAC inhibitors. Understanding the role of dietary procyanidins in HDAC inhibition is important in exploring the therapeutic potential of natural products. METHODS C57BL/6 mice were gavaged with vehicle (water) or grape seed procyanidin extract (GSPE, 250 mg/kg) and terminated 14 h later. Liver and serum were harvested to assess the effect of GSPE on HDAC activity, histone acetylation, Pparα activity and target-gene expression, and serum lipid levels. RESULTS GSPE increased histone acetylation and decreased Class I HDAC activity in vivo, and dose-dependently inhibited recombinant HDAC2 and 3 activities in vitro. Accordingly, Pparα gene and phosphorylated protein expression were increased, as were target genes involved in fatty acid catabolism, suggesting increased Pparα activity. Serum fibroblast growth factor 21 (Fgf21) was elevated, and triglyceride levels were reduced by 28%. CONCLUSION GSPE regulates HDAC and Pparα activities to modulate lipid catabolism and reduce serum triglycerides in vivo.
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Affiliation(s)
- Laura E Downing
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, NV, USA
| | - Bradley S Ferguson
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, NV, USA
| | - Kelvin Rodriguez
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, NV, USA
| | - Marie-Louise Ricketts
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, NV, USA
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Heidker RM, Caiozzi GC, Ricketts ML. Grape Seed Procyanidins and Cholestyramine Differentially Alter Bile Acid and Cholesterol Homeostatic Gene Expression in Mouse Intestine and Liver. PLoS One 2016; 11:e0154305. [PMID: 27111442 PMCID: PMC4844140 DOI: 10.1371/journal.pone.0154305] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2016] [Accepted: 04/12/2016] [Indexed: 01/05/2023] Open
Abstract
Bile acid (BA) sequestrants, lipid-lowering agents, may be prescribed as a monotherapy or combination therapy to reduce the risk of coronary artery disease. Over 33% of adults in the United States use complementary and alternative medicine strategies, and we recently reported that grape seed procyanidin extract (GSPE) reduces enterohepatic BA recirculation as a means to reduce serum triglyceride (TG) levels. The current study was therefore designed to assess the effects on BA, cholesterol and TG homeostatic gene expression following co-administration with GSPE and the BA sequestrant, cholestyramine (CHY). Eight-week old male C57BL/6 mice were treated for 4 weeks with either a control or 2% CHY-supplemented diet, after which, they were administered vehicle or GSPE for 14 hours. Liver and intestines were harvested and gene expression was analyzed. BA, cholesterol, non-esterified fatty acid and TG levels were also analyzed in serum and feces. Results reveal that GSPE treatment alone, and co-administration with CHY, regulates BA, cholesterol and TG metabolism differently than CHY administration alone. Notably, GSPE decreased intestinal apical sodium-dependent bile acid transporter (Asbt) gene expression, while CHY significantly induced expression. Administration with GSPE or CHY robustly induced hepatic BA biosynthetic gene expression, especially cholesterol 7α-hydroxylase (Cyp7a1), compared to control, while co-administration further enhanced expression. Treatment with CHY induced both intestinal and hepatic cholesterologenic gene expression, while co-administration with GSPE attenuated the CHY-induced increase in the liver but not intestine. CHY also induced hepatic lipogenic gene expression, which was attenuated by co-administration with GSPE. Consequently, a 25% decrease in serum TG levels was observed in the CHY+GSPE group, compared to the CHY group. Collectively, this study presents novel evidence demonstrating that GSPE provides additive and complementary efficacy as a lipid-lowering combination therapy in conjunction with CHY by attenuating hepatic cholesterol synthesis, enhancing BA biosynthesis and decreasing lipogenesis, which warrants further investigation.
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Affiliation(s)
- Rebecca M. Heidker
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, Nevada, United States of America
| | - Gianella C. Caiozzi
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, Nevada, United States of America
| | - Marie-Louise Ricketts
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, Nevada, United States of America
- * E-mail:
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Heidker RM, Caiozzi GC, Ricketts ML. Dietary procyanidins selectively modulate intestinal farnesoid X receptor-regulated gene expression to alter enterohepatic bile acid recirculation: elucidation of a novel mechanism to reduce triglyceridemia. Mol Nutr Food Res 2016; 60:727-36. [PMID: 26718753 DOI: 10.1002/mnfr.201500795] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Revised: 12/09/2015] [Accepted: 12/14/2015] [Indexed: 11/09/2022]
Abstract
SCOPE Understanding the molecular basis by which dietary procyanidins modulate triglyceride and cholesterol homeostasis has important implications for the use of natural products in the treatment and prevention of cardiovascular disease. METHODS To determine whether modulation of bile acid (BA) homeostasis contributes to the hypotriglyceridemic action of grape seed procyanidin extract (GSPE) we examined the effect on genes regulating BA absorption, transport and synthesis in vitro, in Caco-2 cells, and in vivo, in wild type (C57BL/6) and farnesoid x receptor knockout (Fxr(-/-)) mice. RESULTS We provide novel evidence demonstrating that GSPE is a naturally occurring gene-selective bile acid receptor modulator (BARM). Mechanistically, GSPE down-regulates genes involved in intestinal BA absorption and transport in an Fxr-dependent manner, resulting in decreased enterohepatic BA recirculation. This correlates with increased fecal BA output, decreased serum triglyceride and cholesterol levels, increased hepatic cholesterol 7α-hydroxylase (Cyp7a1), and decreased intestinal fibroblast growth factor 15 (Fgf15) expression. GSPE also increased hepatic HmgCoA reductase (Hmgcr) and synthase (Hmgcs1) expression, while concomitantly decreasing sterol regulatory element-binding protein 1c (Srebp1c). CONCLUSION GSPE selectively regulates intestinal Fxr-target gene expression in vivo, and modulation of BA absorption and transport is a critical regulatory point for the consequential hypotriglyceridemic effects of GSPE.
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Affiliation(s)
- Rebecca M Heidker
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, Nevada, 89557
| | - Gianella C Caiozzi
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, Nevada, 89557
| | - Marie-Louise Ricketts
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, Nevada, 89557
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Downing LE, Heidker RM, Caiozzi GC, Wong BS, Rodriguez K, Del Rey F, Ricketts ML. A Grape Seed Procyanidin Extract Ameliorates Fructose-Induced Hypertriglyceridemia in Rats via Enhanced Fecal Bile Acid and Cholesterol Excretion and Inhibition of Hepatic Lipogenesis. PLoS One 2015; 10:e0140267. [PMID: 26458107 PMCID: PMC4601771 DOI: 10.1371/journal.pone.0140267] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Accepted: 09/22/2015] [Indexed: 12/31/2022] Open
Abstract
The objective of this study was to determine whether a grape seed procyanidin extract (GSPE) exerts a triglyceride-lowering effect in a hyperlipidemic state using the fructose-fed rat model and to elucidate the underlying molecular mechanisms. Rats were fed either a starch control diet or a diet containing 65% fructose for 8 weeks to induce hypertriglyceridemia. During the 9th week of the study, rats were maintained on their respective diet and administered vehicle or GSPE via oral gavage for 7 days. Fructose increased serum triglyceride levels by 171% after 9 weeks, compared to control, while GSPE administration attenuated this effect, resulting in a 41% decrease. GSPE inhibited hepatic lipogenesis via down-regulation of sterol regulatory element binding protein 1c and stearoyl-CoA desaturase 1 in the fructose-fed animals. GSPE increased fecal bile acid and total lipid excretion, decreased serum bile acid levels and increased the expression of genes involved in cholesterol synthesis. However, bile acid biosynthetic gene expression was not increased in the presence of GSPE and fructose. Serum cholesterol levels remained constant, while hepatic cholesterol levels decreased. GSPE did not modulate expression of genes responsible for esterification or biliary export of the newly synthesized cholesterol, but did increase fecal cholesterol excretion, suggesting that in the presence of GSPE and fructose, the liver may secrete more free cholesterol into the plasma which may then be shunted to the proximal small intestine for direct basolateral to apical secretion and subsequent fecal excretion. Our results demonstrate that GSPE effectively lowers serum triglyceride levels in fructose-fed rats after one week administration. This study provides novel insight into the mechanistic actions of GSPE in treating hypertriglyceridemia and demonstrates that it targets hepatic de novo lipogenesis, bile acid homeostasis and non-biliary cholesterol excretion as important mechanisms for reducing hypertriglyceridemia and hepatic lipid accumulation in the presence of fructose.
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Affiliation(s)
- Laura E. Downing
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, Nevada, United States of America
| | - Rebecca M. Heidker
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, Nevada, United States of America
| | - Gianella C. Caiozzi
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, Nevada, United States of America
| | - Brian S. Wong
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, Nevada, United States of America
| | - Kelvin Rodriguez
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, Nevada, United States of America
| | - Fernando Del Rey
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, Nevada, United States of America
| | - Marie-Louise Ricketts
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, Nevada, United States of America
- * E-mail:
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Del Bas JM, Crescenti A, Arola-Arnal A, Oms-Oliu G, Arola L, Caimari A. Intake of grape procyanidins during gestation and lactation impairs reverse cholesterol transport and increases atherogenic risk indexes in adult offspring. J Nutr Biochem 2015; 26:1670-7. [PMID: 26365577 DOI: 10.1016/j.jnutbio.2015.08.015] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Revised: 08/07/2015] [Accepted: 08/08/2015] [Indexed: 11/16/2022]
Abstract
Cardiovascular disease (CVD) is one of the most prevalent noncommunicable diseases in humans. Different studies have identified dietary procyanidins as bioactive compounds with beneficial properties against CVD by improving lipid homeostasis, among other mechanisms. The aim of this work was to assess whether grape seed procyanidin consumption at a physiological dose during the perinatal period could influence the CVD risk of the offspring. Wistar rat dams were treated with a grape seed procyanidin extract (GSPE; 25mg/kg of body weight per day) or vehicle during gestation and lactation. The adult male offspring of GSPE-treated dams presented decreased high-density lipoprotein cholesterol (HDL-C) levels, increased total cholesterol-to-HDL-C ratios and an exacerbated fasting triglyceride-to-HDL-C ratios (atherogenic index of plasma) compared to the control group. Impaired reverse cholesterol transport (RCT) was evidenced by the accumulation of cholesterol in skeletal muscle and by decreased fecal excretion of cholesterol and bile acids, which was consistent with the observed mRNA down-regulation of the rate-limiting enzyme in the hepatic bile acid synthesis pathway Cyp7A1. Conversely, GSPE programming also resulted in up-regulated gene expression of different key components of the RCT process, such as hepatic Npc1, Abcg1, Abca1, Lxra, Srebp2, Lcat, Scarb1 and Pltp, and the repression of microRNA miR-33a expression, a key negative controller of hepatic RCT at the gene expression level. Our results show that maternal intake of grape procyanidins during the perinatal period impacts different components of the RCT process, resulting in increased CVD risk in the adult offspring.
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Affiliation(s)
- Josep Maria Del Bas
- Grup de Recerca en Nutrició i Salut, Centre Tecnològic de Nutrició i Salut, TECNIO, CEICS, Reus, Spain.
| | - Anna Crescenti
- Grup de Recerca en Nutrició i Salut, Centre Tecnològic de Nutrició i Salut, TECNIO, CEICS, Reus, Spain
| | - Anna Arola-Arnal
- Nutrigenomics Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Tarragona, Spain
| | - Gemma Oms-Oliu
- Department of Food Technology, University of Lleida, Lleida, Spain
| | - Lluís Arola
- Nutrigenomics Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Tarragona, Spain; Centre Tecnològic de Nutrició i Salut, TECNIO, CEICS, Reus, Spain
| | - Antoni Caimari
- Grup de Recerca en Nutrició i Salut, Centre Tecnològic de Nutrició i Salut, TECNIO, CEICS, Reus, Spain
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Pisonero-Vaquero S, Martínez-Ferreras Á, García-Mediavilla MV, Martínez-Flórez S, Fernández A, Benet M, Olcoz JL, Jover R, González-Gallego J, Sánchez-Campos S. Quercetin ameliorates dysregulation of lipid metabolism genes via the PI3K/AKT pathway in a diet-induced mouse model of nonalcoholic fatty liver disease. Mol Nutr Food Res 2015; 59:879-93. [PMID: 25712622 DOI: 10.1002/mnfr.201400913] [Citation(s) in RCA: 92] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Revised: 02/03/2015] [Accepted: 02/09/2015] [Indexed: 12/12/2022]
Abstract
SCOPE Flavonoids and related compounds seem to have favorable effects on nonalcoholic fatty liver disease (NAFLD) progression, although the exact mechanisms implicated are poorly understood. In this study, we aimed to investigate the effect of the flanovol quercetin on gene expression deregulation involved in the development of NAFLD, as well as the possible implication of phosphatidylinositol 3-kinase (PI3K)/AKT pathway modulation. METHODS AND RESULTS We used an in vivo model based on methionine- and choline-deficient (MCD) diet-fed mice and an in vitro model consisting of Huh7 cells incubated with MCD medium. MCD-fed mice showed classical pathophysiological characteristics of nonalcoholic steatohepatitis, associated with altered transcriptional regulation of fatty acid uptake- and trafficking-related gene expression, with increased lipoperoxidation. PI3K/AKT pathway was activated by MCD and triggered gene deregulation causing either activation or inhibition of all studied genes as demonstrated through cell incubation with the PI3K-inhibitor LY294002. Treatment with quercetin reduced AKT phosphorylation, and oxidative/nitrosative stress, inflammation and lipid metabolism-related genes displayed a tendency to normalize in both in vivo and in vitro models. CONCLUSION These results place quercetin as a potential therapeutic strategy for preventing NAFLD progression by attenuating gene expression deregulation, at least in part through PI3K/AKT pathway inactivation.
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Ribas-Latre A, Del Bas JM, Baselga-Escudero L, Casanova E, Arola-Arnal A, Salvadó MJ, Bladé C, Arola L. Dietary proanthocyanidins modulate the rhythm of BMAL1 expression and induce RORα transactivation in HepG2 cells. J Funct Foods 2015. [DOI: 10.1016/j.jff.2015.01.017] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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Salvadó MJ, Casanova E, Fernández-Iglesias A, Arola L, Bladé C. Roles of proanthocyanidin rich extracts in obesity. Food Funct 2015; 6:1053-71. [DOI: 10.1039/c4fo01035c] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Obesity is a multifactorial disorder involving an abnormal or excessive amount of body fat.
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Affiliation(s)
- M. Josepa Salvadó
- Departament de Bioquímica i Biotecnologia
- Universitat Rovira i Virgili
- Tarragona
- Spain
| | - Ester Casanova
- Departament de Bioquímica i Biotecnologia
- Universitat Rovira i Virgili
- Tarragona
- Spain
| | | | - Lluis Arola
- Departament de Bioquímica i Biotecnologia
- Universitat Rovira i Virgili
- Tarragona
- Spain
| | - Cinta Bladé
- Departament de Bioquímica i Biotecnologia
- Universitat Rovira i Virgili
- Tarragona
- Spain
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Margalef M, Guerrero L, Pons Z, Bravo FI, Arola L, Muguerza B, Arola-Arnal A. A dose-response study of the bioavailability of grape seed proanthocyanidin in rat and lipid-lowering effects of generated metabolites in HepG2 cells. Food Res Int 2014; 64:500-507. [PMID: 30011680 DOI: 10.1016/j.foodres.2014.07.019] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2014] [Revised: 07/04/2014] [Accepted: 07/20/2014] [Indexed: 12/19/2022]
Abstract
Hyperlipidemia is one of the principal causes of cardiovascular disease and proanthocyanidins (PAs) regulate lipid homeostasis. This study aims to evaluate the concentration of PAs in rat serum after the administration of different doses of PAs and to determine the capacity of these metabolites to reduce de novolipid synthesis in HepG2 cells. Two hours after oral administration of different doses of a grape seed proanthocyanidin extract (GSPE) (1000, 375, 250 and 125mg/kg), serum was semi-purified and characterised by HPLC-ESI-MS/MS before analysing the synthesis and secretion of lipids in HepG2 cells. Results showed a dose-dependent appearance of metabolised PAs in serum at doses up to 375mg/kg and saturation at 1000mg/kg of GSPE. A reduction in cholesterol esters (CE), free cholesterol (FC) and triglycerides (TG) synthesis was observed without dose-dependence when the cells were treated with PAs metabolites. Moreover, a low dose of metabolites (125mg/kg) was sufficient to reduce FC and TG synthesis. In conclusion, the study demonstrated that PAs metabolise in a dose-dependent manner up to 370mg/kg but not dose-dependent effect was shown in reducing the de novosynthesis of lipids.
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Affiliation(s)
- Maria Margalef
- Nutrigenomic Group, Department of Biochemistry and Biotechnology, Rovira i Virgili University, Tarragona 43007, Spain
| | - Ligia Guerrero
- Nutrigenomic Group, Department of Biochemistry and Biotechnology, Rovira i Virgili University, Tarragona 43007, Spain; Department of Research, Nutrition and Innovation, ALPINA S.A., Bogotá, Colombia
| | - Zara Pons
- Nutrigenomic Group, Department of Biochemistry and Biotechnology, Rovira i Virgili University, Tarragona 43007, Spain
| | - Francisca Isabel Bravo
- Nutrigenomic Group, Department of Biochemistry and Biotechnology, Rovira i Virgili University, Tarragona 43007, Spain
| | - Lluís Arola
- Nutrigenomic Group, Department of Biochemistry and Biotechnology, Rovira i Virgili University, Tarragona 43007, Spain; Centre Tecnològic de Nutrició i Salut (CTNS), TECNIO, CEICS, Reus 43204, Spain
| | - Begoña Muguerza
- Nutrigenomic Group, Department of Biochemistry and Biotechnology, Rovira i Virgili University, Tarragona 43007, Spain; Centre Tecnològic de Nutrició i Salut (CTNS), TECNIO, CEICS, Reus 43204, Spain.
| | - Anna Arola-Arnal
- Nutrigenomic Group, Department of Biochemistry and Biotechnology, Rovira i Virgili University, Tarragona 43007, Spain
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Guerrero L, Margalef M, Pons Z, Quiñones M, Arola L, Arola-Arnal A, Muguerza B. Serum metabolites of proanthocyanidin-administered rats decrease lipid synthesis in HepG2 cells. J Nutr Biochem 2014; 24:2092-9. [PMID: 24231101 DOI: 10.1016/j.jnutbio.2013.08.001] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2013] [Revised: 06/14/2013] [Accepted: 08/01/2013] [Indexed: 12/22/2022]
Abstract
The regular consumption of flavonoids has been associated with reduced mortality and a decreased risk of cardiovascular diseases. The proanthocyanidins found in plasma are very different from the original flavonoids in food sources. The use of physiologically appropriate conjugates of proanthocyanidins is essential for the in vitro analysis of flavonoid bioactivity. In this study, the effect of different proanthocyanidin-rich extracts, which were obtained from cocoa (CCX), French maritime pine bark (Pycnogenol extract, PYC) and grape seed (GSPE), on lipid homeostasis was evaluated. Hepatic human cells (HepG2 cells) were treated with 25 mg/L of CCX, PYC or GSPE. We also performed in vitro experiments to assess the effect on lipid synthesis that is induced by the bioactive GSPE proanthocyanidins using the physiological metabolites that are present in the serum of GSPE-administered rats. For this, Wistar rats were administered 1 g/kg of GSPE, and serum was collected after 2 h. The semipurified serum of GSPE-administered rats was fully characterized by liquid chromatography tandem triple quadrupole mass spectrometry (LC-QqQ/MS(2)). The lipids studied in the analyses were free cholesterol (FC), cholesterol ester (CE) and triglycerides (TG). All three proanthocyanidin-rich extracts induced a remarkable decrease in the de novo lipid synthesis in HepG2 cells. Moreover, GSPE rat serum metabolites reduced the total percentage of CE, FC and particularly TG; this reduction was significantly higher than that observed in the cells directly treated with GSPE. In conclusion, the bioactivity of the physiological metabolites that are present in the serum of rats after their ingestion of a proanthocyanidin-rich extract was demonstrated in Hep G2 cells.
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Affiliation(s)
- Ligia Guerrero
- Department of Biochemistry and Biotechnology, Rovira i Virgili University, Tarragona 43007, Spain; Department of Research, Nutrition and Innovation, ALPINA S.A, Bogotá, Colombia
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Effects of Lotus Root (the Edible Rhizome ofNelumbo nucifera) on the Deveolopment of Non-Alcoholic Fatty Liver Disease in Obese Diabeticdb/dbMice. Biosci Biotechnol Biochem 2014; 76:462-6. [DOI: 10.1271/bbb.110745] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Pons Z, Guerrero L, Margalef M, Arola L, Arola-Arnal A, Muguerza B. Effect of low molecular grape seed proanthocyanidins on blood pressure and lipid homeostasis in cafeteria diet-fed rats. J Physiol Biochem 2014; 70:629-37. [DOI: 10.1007/s13105-014-0329-0] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2013] [Accepted: 02/23/2014] [Indexed: 12/27/2022]
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Flavanol metabolites distribute in visceral adipose depots after a long-term intake of grape seed proanthocyanidin extract in rats. Br J Nutr 2013; 110:1411-20. [DOI: 10.1017/s0007114513000706] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
A considerable number of epidemiological investigations and intervention studies have supported an association between the intake of flavanol- and proanthocyanidin-containing foods and a decreased risk of metabolic diseases. Nonetheless, less is know about the capacity of tissues to accumulate flavanols and/or their metabolites. The main objective of the present study was to determine (n 20) plasma bioavailability and disposition in the liver, muscle, brown adipose tissue (BAT) and white adipose tissues (mesenteric and perirenal) in rats after a long-term consumption of three doses of grape seed phenolic extract (5, 25 and 50 mg/kg body weight) for 21 d in order to determine whether there is a dose–response relationship. Glucuronidated conjugates (total glucuronidated conjugates: C5mg/kg 1·9; C25mg/kg 6·4; C50mg/kg 27·7 μmol/l plasma) followed by methyl glucuronidated conjugates (total methyl glucuronidated conjugates: C5mg/kg 1·98; C25mg/kg 4·48; C50mg/kg 12·5 μmol/l plasma) were the main flavanol metabolites quantified in plasma, also detecting a dimer in its free form (C25mg/kg 0·74; C50mg/kg 0·79 μmol/l plasma). Each of the studied organs has a particular behaviour of accumulation and response to the assayed grape seed extract doses, with an exponential bioavailability–dose relationship in BAT, in which flavanols could play an important role in the reduction or prevention of obesity, modulating the functionality of that tissue.
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Galleano M, Calabro V, Prince PD, Litterio MC, Piotrkowski B, Vazquez-Prieto MA, Miatello RM, Oteiza PI, Fraga CG. Flavonoids and metabolic syndrome. Ann N Y Acad Sci 2012; 1259:87-94. [PMID: 22758640 DOI: 10.1111/j.1749-6632.2012.06511.x] [Citation(s) in RCA: 94] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Increasing evidence indicates that several mechanisms, associated or not with antioxidant actions, are involved in the effects of flavonoids on health. Flavonoid-rich beverages, foods, and extracts, as well as pure flavonoids are studied for the prevention and/or amelioration of metabolic syndrome (MS) and MS-associated diseases. We summarize evidence linking flavonoid consumption with the risk factors defining MS: obesity, hypertriglyceridemia, hypercholesterolemia, hypertension, and insulin resistance. Nevertheless, a number of molecular mechanisms have been identified; the effects of flavonoids modifying major endpoints of MS are still inconclusive. These difficulties are explained by the complex relationships among the risk factors defining MS, the multiple biological targets controlling these risk factors, and the high number of flavonoids (including their metabolites) present in the diet and potentially responsible for the in vivo effects. Consequently, extensive basic and clinical research is warranted to assess the final relevance of flavonoids for MS.
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Affiliation(s)
- Monica Galleano
- Physical Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
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González-Abuín N, Martínez-Micaelo N, Blay M, Pujadas G, Garcia-Vallvé S, Pinent M, Ardévol A. Grape seed-derived procyanidins decrease dipeptidyl-peptidase 4 activity and expression. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2012; 60:9055-9061. [PMID: 22891874 DOI: 10.1021/jf3010349] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
Dipeptidyl-peptidase 4 (DPP4) inhibitors are among the newest treatments against type 2 diabetes. Since some flavonoids modulate DPP4 activity, we evaluated whether grape seed-derived procyanidins (GSPEs), which are antihyperglycemic, modulate DPP4 activity and/or expression. In vitro inhibition assays showed that GSPEs inhibit pure DPP4. Chronic GSPE treatments in intestinal human cells (Caco-2) showed a decrease of DPP4 activity and gene expression. GSPE was also assayed in vivo. Intestinal but not plasmatic DPP4 activity and gene expression were decreased by GSPE in healthy and diet-induced obese animals. Healthy rats also showed glycemia improvement after oral glucose consumption but not after an intraperitoneal glucose challenge. In genetically obese rats, only DPP4 gene expression was down-regulated. Thus, procyanidin inhibition of intestinal DPP4 activity, either directly and/or via gene expression down-regulation, could be responsible for some of their effects in glucose homeostasis.
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Affiliation(s)
- Noemi González-Abuín
- Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Tarragona, Spain
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Baselga-Escudero L, Bladé C, Ribas-Latre A, Casanova E, Salvadó MJ, Arola L, Arola-Arnal A. Grape seed proanthocyanidins repress the hepatic lipid regulators miR-33 and miR-122 in rats. Mol Nutr Food Res 2012; 56:1636-46. [PMID: 22965541 DOI: 10.1002/mnfr.201200237] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2012] [Revised: 07/19/2012] [Accepted: 07/31/2012] [Indexed: 12/18/2022]
Abstract
SCOPE One major health problem in westernized countries is dysregulated fatty acid and cholesterol metabolism that causes pathologies such as metabolic syndrome. Previous studies from our group have shown that proanthocyanidins, which are the most abundant polyphenols in the human diet, regulate lipid metabolism and are potent hypolipidemic agents. The noncoding RNAs, miR-33 and miR-122, regulate genes that are involved in lipid metabolism. METHODS AND RESULTS Here, we show that grape seed proanthocyanidins rapidly and transiently repressed the expression of miR-33 and miR-122 in rat hepatocytes in vivo and in vitro. Furthermore, the miR-33 target gene ATP-binding cassette A1 and the miR-122 target gene fatty acid synthase were also modulated by proanthocyanidins. Specifically, ATP-binding cassette A1 mRNA and protein levels were increased, and fatty acid synthase mRNA and protein levels were reduced after the miRNA levels were altered. CONCLUSION These results suggest that proanthocyanidin treatment increased hepatic cholesterol efflux to produce new HDL particles by repressing miR-33, and it reduced lipogenesis by repressing miR-122. These results highlight a new mechanism by which grape seed proanthocyanidins produce hypolipidemia through their effects on miRNA modulators of lipid metabolism.
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Affiliation(s)
- Laura Baselga-Escudero
- Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain
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Caiozzi G, Wong BS, Ricketts ML. Dietary modification of metabolic pathways via nuclear hormone receptors. Cell Biochem Funct 2012; 30:531-51. [PMID: 23027406 DOI: 10.1002/cbf.2842] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2011] [Revised: 04/07/2012] [Accepted: 05/09/2012] [Indexed: 12/17/2022]
Abstract
Nuclear hormone receptors (NHRs), as ligand-dependent transcription factors, have emerged as important mediators in the control of whole body metabolism. Because of the promiscuous nature of several members of this superfamily that have been found to bind ligand with lower affinity than the classical steroid NHRs, they consequently display a broader ligand selectivity. This promiscuous nature has facilitated various bioactive dietary components being able to act as agonist ligands for certain members of the NHR superfamily. By binding to these NHRs, bioactive dietary components are able to mediate changes in various metabolic pathways, including, glucose, cholesterol and triglyceride homeostasis among others. This review will provide a general overview of the nuclear hormone receptors that have been shown to be activated by dietary components. The physiological consequences of such receptor activation by these dietary components will then be discussed in more detail.
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Affiliation(s)
- Gianella Caiozzi
- Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, NV 89557, USA
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Low doses of grape seed procyanidins reduce adiposity and improve the plasma lipid profile in hamsters. Int J Obes (Lond) 2012; 37:576-83. [PMID: 22584454 DOI: 10.1038/ijo.2012.75] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
OBJECTIVE Procyanidins are polyphenolic compounds with beneficial effects on health in relation to cardiovascular disease and metabolic syndrome. In this study, we evaluated the potential beneficial effects of low doses of a grape seed procyanidin extract (GSPE) on body weight and fat deposition. DESIGN Four groups of hamsters were fed either a standard diet (STD) or a high-fat diet (HFD) for 30 days and supplemented with either GSPE at 25 mg per kg of body weight per day (STD-GSPE and HFD-GSPE groups) or vehicle (STD and HFD groups) during the last 15 days of the study. RESULTS A significant decrease in body weight gain was observed in both GSPE-treated animals at the end of the experiment. GSPE treatment significantly reduced the adiposity index and the weight of all the white adipose tissue depots studied (retroperitoneal (RWAT), mesenteric (MWAT), epididymal (EWAT) and inguinal (IWAT)) in both GSPE-treated groups. GSPE administration reversed the increase in plasma phospholipids induced by the HFD feeding. In the RWAT, GSPE treatment increased the mRNA expression of genes related to β-oxidation and the glycerolipid/free fatty acid (GL/FFA) cycle, mainly in HFD-GSPE animals. In the MWAT, the effects of GSPE at the transcriptional level were not as evident as in the RWAT. Moreover, GSPE treatment induced heparin-releasable lipoprotein lipase activity in the RWAT and MWAT depots. The alterations in the lipid metabolic pathways induced by GSPE were accompanied by lower FFA levels in the plasma and decreased lipid and triglyceride accumulation in the MWAT. CONCLUSION The use of GSPE at low doses protects against fat accumulation and improves the plasma lipid profile in hamsters. We suggest that GSPE exerts these effects in part through the activation of both β-oxidation and the GL/FFA cycle, mainly in the RWAT.
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Moore DD. Nuclear receptors reverse McGarry's vicious cycle to insulin resistance. Cell Metab 2012; 15:615-22. [PMID: 22560214 PMCID: PMC3613429 DOI: 10.1016/j.cmet.2012.03.016] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2011] [Revised: 12/16/2011] [Accepted: 03/08/2012] [Indexed: 12/22/2022]
Abstract
Several pathways and pathologies have been suggested as connections between obesity and diabetes, including inflammation of adipose and other tissues, toxic lipids, endoplasmic reticulum stress, and fatty liver. One specific proposal is that insulin resistance induces a vicious cycle in which hyperinsulinemia increases hepatic lipogenesis and exacerbates fatty liver, in turn further increasing insulin resistance. Here I suggest that reversing this cycle via suppression of the lipogenic transcription factor SREBP-1c is a common thread that connects the antidiabetic effects of a surprising number of nuclear hormone receptors, including CAR, LRH-1, TRβ, ERα, and FXR/SHP.
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Affiliation(s)
- David D Moore
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
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Porez G, Prawitt J, Gross B, Staels B. Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease. J Lipid Res 2012; 53:1723-37. [PMID: 22550135 DOI: 10.1194/jlr.r024794] [Citation(s) in RCA: 224] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Dyslipidemia is an important risk factor for cardiovascular disease (CVD) and atherosclerosis. When dyslipidemia coincides with other metabolic disorders such as obesity, hypertension, and glucose intolerance, defined as the metabolic syndrome (MS), individuals present an elevated risk to develop type 2 diabetes (T2D) as well as CVD. Because the MS epidemic represents a growing public health problem worldwide, the development of therapies remains a major challenge. Alterations of bile acid pool regulation in T2D have revealed a link between bile acid and metabolic homeostasis. The bile acid receptors farnesoid X receptor (FXR) and TGR5 both regulate lipid, glucose, and energy metabolism, rendering them potential pharmacological targets for MS therapy. This review discusses the mechanisms of metabolic regulation by FXR and TGR5 and the utility relevance of natural and synthetic modulators of FXR and TGR5 activity, including bile acid sequestrants, in the treatment of the MS.
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Álvarez E, Rodiño-Janeiro BK, Jerez M, Ucieda-Somoza R, Núñez MJ, González-Juanatey JR. Procyanidins from grape pomace are suitable inhibitors of human endothelial NADPH oxidase. J Cell Biochem 2012; 113:1386-96. [DOI: 10.1002/jcb.24011] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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Abstract
The aim of the present study was to determine the effects of a cafeteria diet on the function and apoptosis of the pancreas, and the activity and expression of the insulin-degrading enzyme (IDE). Female Wistar rats were fed either with a cafeteria diet or a control diet for 17 weeks, and blood and tissues were then collected for analysis. The cafeteria diet-treated rats had higher plasma insulin and C-peptide levels (P<0·05), showing increased insulin secretion by the pancreas. Insulin protein and gene expression levels were higher in the pancreas of obese rats, as was its transcriptional controller, pancreatic duodenal homeobox 1 (P<0·05). Feeding a cafeteria diet down-regulated the gene expression of the anti-apoptotic marker B-cell/lymphoma 2 (BCL2), and up-regulated the protein levels of BCL2-associated X protein, a pro-apoptotic marker (P<0·05). The cafeteria diet caused lipid accumulation in the pancreas and modified the expression of key genes that control lipid metabolism. To assay whether insulin clearance was also modified, we checked the activity of the IDE, one of the enzymes responsible for insulin clearance. We found increased liver IDE activity (P<0·05) in the cafeteria diet-fed animals, which could, in part, be due to an up-regulation of its gene expression. Conversely, IDE gene expression was unmodified in the kidney and adipose tissue; although when the adipose tissue weight was considered, the insulin clearance potential was higher in the cafeteria diet-treated rats. In conclusion, treatment with a cafeteria diet for 17 weeks in rats mimicked a pre-diabetic state, with ectopic lipid accumulation in the pancreas, and increased the IDE-mediated insulin clearance capability.
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Effect of Vaccinium ashei reade leaf extracts on lipid metabolism in obese OLETF rats. Biosci Biotechnol Biochem 2011; 75:2304-8. [PMID: 22146710 DOI: 10.1271/bbb.110451] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The effects of a hot water extract and fractional extracts from rabbiteye blueberry (Vaccinium ashei reade) leaves (BBL) on lipid metabolism were studied in obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Feeding the hot water extract and fractional extracts from BBL alleviated hepatic triglyceride accumulation in the rats. Additionally, feeding with the flavonol glycoside (FG) and proanthocyanidin (PA) fractions lowered serum cholesterol levels in the obese rats. The results from measurements of the hepatic enzyme activity indicate that the hypolipidemic effects of the hot water extract and the PA fraction might be attributable to enhanced lipolysis in the liver. The reduced serum levels of C-reactive protein, an inflammatory cytokine, by the chlorogenic acid + rutin fraction and FG fraction might be associated with alleviating the metabolic abnormalities in obese rats. These results indicate that the BBL extracts, and especially FG and PA, exerted hypolipidemic effects on obese OLETF rats and suggest that an infusion of BBL can be useful as a dietary hypolipidemic component.
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Quesada H, Pajuelo D, Fernández-Iglesias A, Díaz S, Ardevol A, Blay M, Salvadó M, Arola L, Blade C. Proanthocyanidins modulate triglyceride secretion by repressing the expression of long chain acyl-CoA synthetases in Caco2 intestinal cells. Food Chem 2011. [DOI: 10.1016/j.foodchem.2011.05.125] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Tsuruta Y, Nagao K, Kai S, Tsuge K, Yoshimura T, Koganemaru K, Yanagita T. Polyphenolic extract of lotus root (edible rhizome of Nelumbo nucifera) alleviates hepatic steatosis in obese diabetic db/db mice. Lipids Health Dis 2011; 10:202. [PMID: 22067945 PMCID: PMC3228742 DOI: 10.1186/1476-511x-10-202] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2011] [Accepted: 11/09/2011] [Indexed: 12/18/2022] Open
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease of industrialized countries. Thus, discovering food components that can ameliorate NAFLD is of interest. Lotus root, the edible rhizome of Nelumbo nucifera, contains high levels of polyphenolic compounds, and several health-promoting properties of lotus root have been reported. In this study, we tested whether feeding a polyphenolic extract of lotus root to db/db mice protects them from hepatic steatosis. Results After 3 weeks of feeding, the hepatomegaly and hepatic triglyceride accumulation were markedly alleviated in the lotus polyphenol-diet-fed db/db mice relative to the control mice. Although the lipolytic enzyme activity was not changed, the activities of lipogenic enzymes, such as fatty acid synthase and malic enzyme, were significantly lower in the lotus polyphenol diet-fed db/db mice. Additionally, the ESI-IT/MS and MALDI-TOF MS spectra revealed the presence of B-type proanthocyanidin polymers with polymerization degree up to 9 in the polyphenolic lotus root extract. Conclusion We speculate that the condensed tannins contained in lotus root can alleviate hepatic steatosis by suppressing the lipogenic enzyme activity in the livers of db/db mice.
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Affiliation(s)
- Yumi Tsuruta
- Department of Applied Biochemistry and Food Science, Saga University, Saga 840-8502, Japan
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The lipid-lowering effect of dietary proanthocyanidins in rats involves both chylomicron-rich and VLDL-rich fractions. Br J Nutr 2011; 108:208-17. [DOI: 10.1017/s0007114511005472] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Proanthocyanidins have been shown to improve postprandial hypertriacylglycerolaemia. The present study aims to determine the actual contribution of chylomicrons (CM) and VLDL in the hypotriacylglycerolaemic action of grape seed proanthocyanidin extract (GSPE) in the postprandial state and to characterise the mechanisms by which the GSPE treatment reduces TAG-rich lipoproteins in vivo. A plasma lipid tolerance test was performed on rats fasted for 14 h and orally loaded with lard containing either GSPE or not. GSPE (250 mg/kg body weight) markedly blocked the increase in plasma TAG induced by lard, with a statistically significant reduction of 22 % in the area under the curve. The VLDL-rich fraction was the major contributor (72 %) after 1 h, whereas the CM-rich fraction was the major contributor (85 %) after 3 h. At 5 and 7 h after treatment, CM-rich and VLDL-rich fractions showed a similar influence. Plasma post-heparin lipoprotein lipase (LPL) activity and LPL mRNA levels in white adipose tissue and muscle were not affected by GSPE. On the contrary, GSPE treatment significantly repressed (30 %) the secretion of VLDL-TAG. In the liver, GSPE treatment induced different effects on the expression of acyl-coenzyme A synthetase long-chain family member 1, Apoc3 and 3-hydroxy-3-methylglutaryl-coenzyme A reductase at 1 h and Cd36 at 5 h, compared to those induced by lard. Furthermore, GSPE treatment significantly increased the activity of carnitine palmitoyltransferase 1a at 1 h. In conclusion, both CM-rich and VLDL-rich fractions contributed to the hypotriacylglycerolaemic action of GSPE, but their influence depended on time. GSPE induces hypotriacylglycerolaemic actions by repressing lipoprotein secretion and not by increasing LPL activity.
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