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Borja-Magno AI, Furuzawa-Carballeda J, Guevara-Cruz M, Arias C, Granados J, Bourges H, Tovar AR, Sears B, Noriega LG, Gómez FE. Supplementation with EPA and DHA omega-3 fatty acids improves peripheral immune cell mitochondrial dysfunction and inflammation in subjects with obesity. J Nutr Biochem 2023; 120:109415. [PMID: 37437746 DOI: 10.1016/j.jnutbio.2023.109415] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 07/01/2023] [Accepted: 07/07/2023] [Indexed: 07/14/2023]
Abstract
Omega-3 fatty acids (w-3 FA) have anti-inflammatory effects and improve mitochondrial function. Nonetheless, little is known about their effect on mitochondrial bioenergetics of peripheral blood mononuclear cells (PBMCs) in individuals with obesity. Thus, this study aimed to determine the mitochondrial bioenergetics status and cell subset composition of PBMCs during obesity, before and after 1 month supplementation with w-3 FA. We performed a case-control study with twelve women with normal BMI (lean group) and 19 with grade 2 obesity (obese group), followed by a before-after prospective study where twelve subjects with obesity received a 1 month intervention with 5.25 g of w-3 FA (3.5 g eicosapentaenoic (EPA) and 1.75 g docosahexaenoic (DHA) acids), and obtained PBMCs from all participants. Mitochondrial bioenergetic markers, including basal and ATP-production associated respiration, proton leak, and nonmitochondrial respiration, were higher in PBMCs from the obese group vs. the lean group. The bioenergetic health index (BHI), a marker of mitochondrial function, was lower in the obese vs. the lean group. In addition, Th1, Th2, Th17, CD4+ Tregs, CD8+ Tregs, and Bregs, M1 monocytes and pDCreg cells were higher in PBMCs from the obese group vs. the lean group. The w-3 FA intervention improved mitochondrial function, mainly by decreasing nonmitochondrial respiration and increasing the reserve respiratory capacity and BHI. The intervention also reduced circulating pro-inflammatory and anti-inflammatory lymphocyte and monocytes subsets in individuals with obesity. The mitochondrial dysfunction of PBMCs and the higher proportion of peripheral pro-inflammatory and anti-inflammatory immune cells in subjects with obesity, improved with 1 month supplementation with EPA and DHA.
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Affiliation(s)
- Angélica I Borja-Magno
- Department of Nutritional Physiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Ciudad de México, Mexico
| | - Janette Furuzawa-Carballeda
- Department of Experimental Surgery, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Ciudad de México, Mexico
| | - Martha Guevara-Cruz
- Department of Nutritional Physiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Ciudad de México, Mexico
| | - Clorinda Arias
- Department of Genomics Medicine and Environmental Toxicology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Coyoacan, Ciudad de México, Mexico
| | - Julio Granados
- Department of Transplants, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Ciudad de México, Mexico
| | - Hector Bourges
- Divission of Nutrition, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Ciudad de México, Mexico
| | - Armando R Tovar
- Department of Nutritional Physiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Ciudad de México, Mexico
| | - Barry Sears
- Inflammation Research Foundation, Peabody, Massachusetts, USA
| | - Lilia G Noriega
- Department of Nutritional Physiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Ciudad de México, Mexico.
| | - Francisco Enrique Gómez
- Department of Nutritional Physiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Ciudad de México, Mexico.
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Yu T, Wang L, Zhang L, Deuster PA. Mitochondrial Fission as a Therapeutic Target for Metabolic Diseases: Insights into Antioxidant Strategies. Antioxidants (Basel) 2023; 12:1163. [PMID: 37371893 DOI: 10.3390/antiox12061163] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 05/22/2023] [Accepted: 05/25/2023] [Indexed: 06/29/2023] Open
Abstract
Mitochondrial fission is a crucial process in maintaining metabolic homeostasis in normal physiology and under conditions of stress. Its dysregulation has been associated with several metabolic diseases, including, but not limited to, obesity, type 2 diabetes (T2DM), and cardiovascular diseases. Reactive oxygen species (ROS) serve a vital role in the genesis of these conditions, and mitochondria are both the main sites of ROS production and the primary targets of ROS. In this review, we explore the physiological and pathological roles of mitochondrial fission, its regulation by dynamin-related protein 1 (Drp1), and the interplay between ROS and mitochondria in health and metabolic diseases. We also discuss the potential therapeutic strategies of targeting mitochondrial fission through antioxidant treatments for ROS-induced conditions, including the effects of lifestyle interventions, dietary supplements, and chemicals, such as mitochondrial division inhibitor-1 (Mdivi-1) and other mitochondrial fission inhibitors, as well as certain commonly used drugs for metabolic diseases. This review highlights the importance of understanding the role of mitochondrial fission in health and metabolic diseases, and the potential of targeting mitochondrial fission as a therapeutic approach to protecting against these conditions.
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Affiliation(s)
- Tianzheng Yu
- Consortium for Health and Military Performance, Department of Military and Emergency Medicine, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, MD 20814, USA
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA
| | - Li Wang
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA
- Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
- Department of Pathology, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, MD 20814, USA
| | - Lei Zhang
- Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
| | - Patricia A Deuster
- Consortium for Health and Military Performance, Department of Military and Emergency Medicine, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, MD 20814, USA
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Damman CJ. Perspective: Nutrition’s Next Chapter – Bioactive Gaps & the Microbiome-Mitochondria Axis. Adv Nutr 2023; 14:420-425. [PMID: 37011764 DOI: 10.1016/j.advnut.2023.03.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 03/03/2023] [Accepted: 03/30/2023] [Indexed: 04/03/2023] Open
Abstract
Food has the power to heal. Our bodies transform and are transformed by the elements in food and the adage that we are what we eat is figuratively and literally true. Twentieth century nutrition science focused on decoding the processes and building blocks of this transformation -- the proteins, fats, carbohydrates, vitamins, and minerals. Twenty-first century nutrition science is aimed at better understanding the increasingly appreciated bioactives within the food matrix that help regulate this transformation - fibers, phytonutrients, bioactive fats, and ferments. Our microbiome and the mitochondria play a key function in orchestrating the role of bioactives in health and are inspiring next-generation nutritional approaches for addressing over- and undernutrition.
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Xiao T, Guo Z, Fu M, Huang J, Wang X, Zhao Y, Tao L, Shen X. Amelioration of Alcoholic Liver Disease by Activating PXR-Cytochrome P450s Axis with Blackberry Extract. SEPARATIONS 2022; 9:321. [DOI: 10.3390/separations9100321] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2025] Open
Abstract
Blackberry is widely used in diets for its rich biological phytochemicals and health benefits. However, the relationship between the effect of blackberry extract (BBE) on ameliorating alcoholic liver disease (ALD) and the PXR-Cytochrome P450s axis in vivo and in vitro is unknown. In this study, 50% and 30% ethanol by gavage were used to establish acute and subacute ALD. Male mice were intragastrically administered BBE with 25, 50, and 100 mg/kg BW in the treatment groups. In the experiment, samples were collected, and related indices and histopathological observation were measured. In addition, the potential mechanism was predicted by network and docking studies, which were verified by qRT-PCR analysis, the detection of apoptosis, the measurement of mitochondrial membrane potential, the detection of ROS levels, and Western blotting in liver tissues and HepG2 cells. The acute and subacute ALD experiments indicated BBE ameliorated liver indices, AST, ALT, SOD, and MDA in serum, and the histopathology changed, as observed via H&E, Sirius red, and oil red O staining. The potential mechanism was predicted by network and docking studies, which were verified by experiments. Western blotting suggested BBE reduced the protein expression of NF-κB, TGF-β, IL-6, and α-SMA, and enhanced PXR and CAR in livers. In addition, qRT-PCR showed BBE significantly elevated the mRNA levels of PXR, CAR, CYP3A25, CYP3A11, and CYP2B10. In the experiment of the ethanol-induced apoptosis of HepG2 cells, BBE reduced the apoptosis of HepG2 cells by boosting mitochondrial membrane potential, reducing the apoptotic rate and ROS content, lessening the expression of Bax, and inducing the expression of PXR. For the first time, this study demonstrated BBE’s preventive effects on ALD, which are associated with the antioxidation and stimulation of the PXR-Cytochrome P450s axis. In addition, BBE is available as a nutritional agent.
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Affiliation(s)
- Ting Xiao
- The State Key Laboratory of Functions and Applications of Medicinal Plants, The Department of Pharmaceutic Preparation of Chinse Medicine, The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China
- The Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, China
| | - Zhenghong Guo
- School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
| | - Min Fu
- The Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, China
| | - Jiaoyan Huang
- The Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, China
| | - Xiaowei Wang
- The Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, China
| | - Yuqing Zhao
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Ling Tao
- The State Key Laboratory of Functions and Applications of Medicinal Plants, The Department of Pharmaceutic Preparation of Chinse Medicine, The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China
- The Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, China
| | - Xiangchun Shen
- The State Key Laboratory of Functions and Applications of Medicinal Plants, The Department of Pharmaceutic Preparation of Chinse Medicine, The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China
- The Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, China
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Chen H, Dai H, Zhu H, Ma L, Fu Y, Feng X, Sun Y, Zhang Y. Construction of dual-compartmental micro-droplet via shrimp ferritin nanocages stabilized Pickering emulsions for co-encapsulation of hydrophobic/hydrophilic bioactive compounds. Food Hydrocoll 2022. [DOI: 10.1016/j.foodhyd.2021.107443] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Wang Z, Yang Z, Liu J, Hao Y, Sun B, Wang J. Potential Health Benefits of Whole Grains: Modulation of Mitochondrial Biogenesis and Energy Metabolism. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:14065-14074. [PMID: 34775748 DOI: 10.1021/acs.jafc.1c05527] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Mitochondria play an essential role in maintaining cellular metabolic homeostasis. However, its dysfunction will cause different pathophysiological consequences. A specific mechanism of action has been developed by cells to adapt to changes in physiological conditions or in response to different stimuli, by meditating mitochondrial number, structure, and energy metabolism. Whole grains are considered healthier than refined grains for their higher amounts of bioactive components, with proven multiple health benefits. The modulation of an appropriate mitochondrial function contributes to the bioactive-component-based health improvements. Thus, this review aims to represent current studies that identify the impact of natural bioactive components in whole grains against metabolic disorders by modulating mitochondrial biogenesis and energy metabolism. It seems most attractive to aim nutritional intervention at the prevention or treatment of metabolic abnormalities and hence to target dietary management at improvement of mitochondrial function.
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Affiliation(s)
- Ziyuan Wang
- China-Canada Joint Lab of Food Nutrition and Health (Beijing), Beijing Technology & Business University, Beijing 100048, People's Republic of China
| | - Zihui Yang
- China-Canada Joint Lab of Food Nutrition and Health (Beijing), Beijing Technology & Business University, Beijing 100048, People's Republic of China
| | - Jie Liu
- China-Canada Joint Lab of Food Nutrition and Health (Beijing), Beijing Technology & Business University, Beijing 100048, People's Republic of China
| | - Yiming Hao
- China-Canada Joint Lab of Food Nutrition and Health (Beijing), Beijing Technology & Business University, Beijing 100048, People's Republic of China
| | - Baoguo Sun
- China-Canada Joint Lab of Food Nutrition and Health (Beijing), Beijing Technology & Business University, Beijing 100048, People's Republic of China
| | - Jing Wang
- China-Canada Joint Lab of Food Nutrition and Health (Beijing), Beijing Technology & Business University, Beijing 100048, People's Republic of China
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7
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Nunes S, Viana SD, Preguiça I, Alves A, Fernandes R, Teodoro JS, Matos P, Figueirinha A, Salgueiro L, André A, Silva S, Jarak I, Carvalho RA, Cavadas C, Rolo AP, Palmeira CM, Pintado MM, Reis F. Blueberry Counteracts Prediabetes in a Hypercaloric Diet-Induced Rat Model and Rescues Hepatic Mitochondrial Bioenergetics. Nutrients 2021; 13:4192. [PMID: 34959746 PMCID: PMC8706913 DOI: 10.3390/nu13124192] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 11/19/2021] [Accepted: 11/20/2021] [Indexed: 12/11/2022] Open
Abstract
The paramount importance of a healthy diet in the prevention of type 2 diabetes is now well recognized. Blueberries (BBs) have been described as attractive functional fruits for this purpose. This study aimed to elucidate the cellular and molecular mechanisms pertaining to the protective impact of blueberry juice (BJ) on prediabetes. Using a hypercaloric diet-induced prediabetic rat model, we evaluated the effects of BJ on glucose, insulin, and lipid profiles; gut microbiota composition; intestinal barrier integrity; and metabolic endotoxemia, as well as on hepatic metabolic surrogates, including several related to mitochondria bioenergetics. BJ supplementation for 14 weeks counteracted diet-evoked metabolic deregulation, improving glucose tolerance, insulin sensitivity, and hypertriglyceridemia, along with systemic and hepatic antioxidant properties, without a significant impact on the gut microbiota composition and related mechanisms. In addition, BJ treatment effectively alleviated hepatic steatosis and mitochondrial dysfunction observed in the prediabetic animals, as suggested by the amelioration of bioenergetics parameters and key targets of inflammation, insulin signaling, ketogenesis, and fatty acids oxidation. In conclusion, the beneficial metabolic impact of BJ in prediabetes may be mainly explained by the rescue of hepatic mitochondrial bioenergetics. These findings pave the way to support the use of BJ in prediabetes to prevent diabetes and its complications.
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Affiliation(s)
- Sara Nunes
- Institute of Pharmacology & Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; (S.N.); (S.D.V.); (I.P.); (A.A.); (R.F.)
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal;
- Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal
| | - Sofia D. Viana
- Institute of Pharmacology & Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; (S.N.); (S.D.V.); (I.P.); (A.A.); (R.F.)
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal;
- Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal
- Polytechnic Institute of Coimbra, ESTESC-Coimbra Health School, Pharmacy/Biomedical Laboratory Sciences, 3046-854 Coimbra, Portugal;
| | - Inês Preguiça
- Institute of Pharmacology & Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; (S.N.); (S.D.V.); (I.P.); (A.A.); (R.F.)
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal;
- Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal
| | - André Alves
- Institute of Pharmacology & Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; (S.N.); (S.D.V.); (I.P.); (A.A.); (R.F.)
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal;
- Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal
| | - Rosa Fernandes
- Institute of Pharmacology & Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; (S.N.); (S.D.V.); (I.P.); (A.A.); (R.F.)
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal;
- Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal
| | - João S. Teodoro
- Department of Life Sciences, Faculty of Science and Technology (FCTUC), University of Coimbra, 3000-456 Coimbra, Portugal; (J.S.T.); (R.A.C.); (A.P.R.); (C.M.P.)
- Center for Neurosciences and Cell Biology of Coimbra (CNC), University of Coimbra, 3004-504 Coimbra, Portugal
| | - Patrícia Matos
- Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; (P.M.); (A.F.); (L.S.)
- LAQV, REQUIMTE, Faculty of Pharmacy, University of Coimbra, 3000-456 Coimbra, Portugal
- CIEPQPF, Chemical Process Engineering and Forest Products Research Centre Research Center, University of Coimbra, 3000-456 Coimbra, Portugal
| | - Artur Figueirinha
- Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; (P.M.); (A.F.); (L.S.)
- LAQV, REQUIMTE, Faculty of Pharmacy, University of Coimbra, 3000-456 Coimbra, Portugal
| | - Lígia Salgueiro
- Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; (P.M.); (A.F.); (L.S.)
- CIEPQPF, Chemical Process Engineering and Forest Products Research Centre Research Center, University of Coimbra, 3000-456 Coimbra, Portugal
| | - Alexandra André
- Polytechnic Institute of Coimbra, ESTESC-Coimbra Health School, Pharmacy/Biomedical Laboratory Sciences, 3046-854 Coimbra, Portugal;
| | - Sara Silva
- CBQF—Centro de Biotecnologia e Química Fina—Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal; (S.S.); (M.M.P.)
| | - Ivana Jarak
- Department of Microscopy, Laboratory of Cell Biology and Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal;
| | - Rui A. Carvalho
- Department of Life Sciences, Faculty of Science and Technology (FCTUC), University of Coimbra, 3000-456 Coimbra, Portugal; (J.S.T.); (R.A.C.); (A.P.R.); (C.M.P.)
- Associated Laboratory for Green Chemistry-Clean Technologies and Processes, REQUIMTE, Faculty of Sciences and Technology, University of Porto, 4050-313 Porto, Portugal
| | - Cláudia Cavadas
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal;
- Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal
- Center for Neurosciences and Cell Biology of Coimbra (CNC), University of Coimbra, 3004-504 Coimbra, Portugal
- Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; (P.M.); (A.F.); (L.S.)
| | - Anabela P. Rolo
- Department of Life Sciences, Faculty of Science and Technology (FCTUC), University of Coimbra, 3000-456 Coimbra, Portugal; (J.S.T.); (R.A.C.); (A.P.R.); (C.M.P.)
- Center for Neurosciences and Cell Biology of Coimbra (CNC), University of Coimbra, 3004-504 Coimbra, Portugal
| | - Carlos M. Palmeira
- Department of Life Sciences, Faculty of Science and Technology (FCTUC), University of Coimbra, 3000-456 Coimbra, Portugal; (J.S.T.); (R.A.C.); (A.P.R.); (C.M.P.)
- Center for Neurosciences and Cell Biology of Coimbra (CNC), University of Coimbra, 3004-504 Coimbra, Portugal
| | - Maria M. Pintado
- CBQF—Centro de Biotecnologia e Química Fina—Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal; (S.S.); (M.M.P.)
| | - Flávio Reis
- Institute of Pharmacology & Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; (S.N.); (S.D.V.); (I.P.); (A.A.); (R.F.)
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal;
- Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal
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8
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Sotiropoulou M, Katsaros I, Vailas M, Lidoriki I, Papatheodoridis GV, Kostomitsopoulos NG, Valsami G, Tsaroucha A, Schizas D. Nonalcoholic fatty liver disease: The role of quercetin and its therapeutic implications. Saudi J Gastroenterol 2021; 27:319-330. [PMID: 34810376 PMCID: PMC8656328 DOI: 10.4103/sjg.sjg_249_21] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 08/29/2021] [Accepted: 09/14/2021] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease, affecting almost one-third of the general population and 75% of obese patients with type 2 diabetes. The aim of this article is to review the current evidence concerning the role of quercetin, a natural compound and flavonoid, and its possible therapeutic effects on this modern-day disease. Despite the fact that the exact pathophysiological mechanisms through which quercetin has a hepatoprotective effect on NAFLD are still not fully elucidated, this review clearly demonstrates that this flavonoid has potent antioxidative stress action and inhibitory effects on hepatocyte apoptosis, inflammation, and generation of reactive oxygen species, factors which are linked to the development of the disease. NAFLD is closely associated with increased dietary fat consumption, especially in Western countries. The hepatoprotective effect of quercetin against NAFLD merits serious consideration and further validation by future studies.
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Affiliation(s)
- Maria Sotiropoulou
- Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Ioannis Katsaros
- Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Michail Vailas
- Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Irene Lidoriki
- Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Nikolaos G Kostomitsopoulos
- Center of Clinical, Experimental Surgery, and Translational Research, Biomedical Research Foundation, Academy of Athens, Athens, Greece
| | - Georgia Valsami
- Department of Pharmacy, Laboratory of Biopharmaceutics-Pharmacokinetics, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece
| | - Alexandra Tsaroucha
- Laboratory of Experimental Surgery, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
| | - Dimitrios Schizas
- Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
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9
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Vásquez-Reyes S, Velázquez-Villegas LA, Vargas-Castillo A, Noriega LG, Torres N, Tovar AR. Dietary bioactive compounds as modulators of mitochondrial function. J Nutr Biochem 2021; 96:108768. [PMID: 34000412 DOI: 10.1016/j.jnutbio.2021.108768] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 02/25/2021] [Accepted: 04/21/2021] [Indexed: 01/11/2023]
Abstract
The increase in incidence and prevalence of metabolic diseases, such as diabetes, obesity, and metabolic syndrome, is a health problem worldwide. Nutritional strategies that can impact on mitochondrial activity represent a novel and effective option to modulate energy expenditure and energetic metabolism in cells and tissues and could be used as adjuvant treatments for metabolic-associated disorders. Dietary bioactive compounds also known as "food bioactives" have proven to exert multiple health benefits and counteract metabolic alterations. In the last years, it has been consistently reported that the modulation of mitochondrial function represents one of the mechanisms behind the bioactive compounds-dependent health improvements. In this review, we focus on gathering, summarizing, and discussing the evidence that supports the effect of dietary bioactive compounds on mitochondrial activity and the relation of these effects in the pathological context. Despite the evidence presented here on in vivo and in vitro effects, more studies are needed to determine their effectiveness in humans.
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Affiliation(s)
- Sarai Vásquez-Reyes
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México CDMX, Mexico
| | - Laura A Velázquez-Villegas
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México CDMX, Mexico
| | - Ariana Vargas-Castillo
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México CDMX, Mexico
| | - Lilia G Noriega
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México CDMX, Mexico
| | - Nimbe Torres
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México CDMX, Mexico
| | - Armando R Tovar
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México CDMX, Mexico.
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10
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Jurado-Fasoli L, Amaro-Gahete FJ, Merchan-Ramirez E, Labayen I, Ruiz JR. Relationships between diet and basal fat oxidation and maximal fat oxidation during exercise in sedentary adults. Nutr Metab Cardiovasc Dis 2021; 31:1087-1101. [PMID: 33549436 DOI: 10.1016/j.numecd.2020.11.021] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 11/06/2020] [Accepted: 11/24/2020] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND AIMS To study the relationships between different dietary factors (i.e., energy, macronutrient and fatty acid intake, food group consumption, and dietary pattern) and basal fat oxidation (BFox) and maximal fat oxidation during exercise (MFO) in sedentary adults. METHOD AND RESULTS A total of 212 (n = 130 women; 32.4 ± 15.1 years) sedentary healthy adults took part in the present study. Information on the different dietary factors examined was gathered through a food frequency questionnaire and three nonconsecutive 24 h recalls. Energy and macronutrient intakes and food consumption were then estimated and dietary patterns calculated. BFox and MFO were measured by indirect calorimetry following standard procedures. Our study shows that dietary fiber intake was positively associated with BFox after taking into consideration the age, sex, and energy intake. A significant positive association between nut consumption and BFox was observed, which became nonsignificant after taking into consideration the age and energy intake. Fat intake and the dietary quality index (DQI), and the DQI for the Mediterranean diet were positively associated with MFO, which was attenuated after taking sex, age, and energy intake into consideration. CONCLUSION A higher dietary fiber intake and fat intake are associated with higher BFox and MFO, respectively, in sedentary adults. CLINICAL TRIALS ClinicalTrials.gov, ID: NCT02365129 (https://clinicaltrials.gov/ct2/show/study/NCT02365129) & ID: NCT03334357 (https://clinicaltrials.gov/ct2/show/NCT03334357).
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Affiliation(s)
- Lucas Jurado-Fasoli
- PROmoting FITness and Health through physical activity research group (PROFITH), Department of Physical Education and Sports, Faculty of Sport Sciences, University of Granada, 18071, Granada, Spain; EFFECTS 262 Research Group, Department of Medical Physiology, School of Medicine. University of Granada, 18071, Granada, Spain.
| | - Francisco J Amaro-Gahete
- PROmoting FITness and Health through physical activity research group (PROFITH), Department of Physical Education and Sports, Faculty of Sport Sciences, University of Granada, 18071, Granada, Spain; EFFECTS 262 Research Group, Department of Medical Physiology, School of Medicine. University of Granada, 18071, Granada, Spain
| | - Elisa Merchan-Ramirez
- PROmoting FITness and Health through physical activity research group (PROFITH), Department of Physical Education and Sports, Faculty of Sport Sciences, University of Granada, 18071, Granada, Spain
| | - Idoia Labayen
- Institute for Innovation & Sustainable Development in Food Chain (IS-FOOD), Public University of Navarra, Campus de Arrosadía, 31008, Pamplona, Spain
| | - Jonatan R Ruiz
- PROmoting FITness and Health through physical activity research group (PROFITH), Department of Physical Education and Sports, Faculty of Sport Sciences, University of Granada, 18071, Granada, Spain
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11
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Diao J, Zhao H, You P, You H, Wu H, Shou X, Cheng G. Rosmarinic acid ameliorated cardiac dysfunction and mitochondrial injury in diabetic cardiomyopathy mice via activation of the SIRT1/PGC-1α pathway. Biochem Biophys Res Commun 2021; 546:29-34. [PMID: 33561745 DOI: 10.1016/j.bbrc.2021.01.086] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 01/25/2021] [Indexed: 02/07/2023]
Abstract
Mitochondrial injury plays an essential role in the pathogenesis of diabetic cardiomyopathy (DCM). Previous studies demonstrated that rosmarinic acid (RA) treatment prevented high glucose-induced mitochondrial injury in vitro. However, whether RA can ameliorate cardiac function by preventing mitochondrial injury in DCM is unknown. The SIRT1/PGC-1α pathway has emerged as an important regulator of metabolic control and other mitochondrial functions. The present study was undertaken to determine the effects of RA on mitochondrial and cardiac function in DCM as well as the involvement of the SIRT1/PGC-1α pathway. Our results revealed that RA improved cardiac systolic and diastolic function and prevented mitochondrial injury in DCM, as shown by the reduced blood glucose and lipid levels, increased mitochondrial membrane potential levels, improved adenosine triphosphate synthesis, and inhibited apoptosis (P < 0.05). Moreover, RA upregulated the expression of SIRT1 and PGC-1α in DCM mice and high glucose-treated H9c2 cardiomyocytes (P < 0.05). Further mechanistic studies in H9c2 cardiomyocytes revealed that suppression of SIRT1 by Sh-SIRT1 counteracted the effects of RA on high glucose-induced abnormal metabolism of glucose and lipids, oxidative stress and apoptosis (P < 0.05). Taken together, these data indicate that RA prevented mitochondrial injury and cardiac dysfunction in DCM mice, and the SIRT1/PGC-1α pathway mediated the protective effects of RA.
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Affiliation(s)
- Jiayu Diao
- Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, China
| | - Hongmou Zhao
- Department of Foot and Ankle Surgery, Xi'an Honghui Hospital, China
| | - Penghua You
- Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, China
| | - Hongjun You
- Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, China
| | - Haoyu Wu
- Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, China
| | - Xiling Shou
- Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, China
| | - Gong Cheng
- Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, China.
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12
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Zakłos-Szyda M, Gałązka-Czarnecka I, Grzelczyk J, Budryn G. Cicer arietinum L. Sprouts' Influence on Mineralization of Saos-2 and Migration of MCF-7 Cells. Molecules 2020; 25:E4490. [PMID: 33007937 PMCID: PMC7583992 DOI: 10.3390/molecules25194490] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 09/25/2020] [Accepted: 09/28/2020] [Indexed: 01/04/2023] Open
Abstract
In the present study, we investigated the biological activity of four extracts obtained from Cicer arietinum L. sprouts. The fermentation of the sprouts with Lactobacillus casei and their incubation with β-glucosidase elevated the concentrations of isoflavonoids, especially coumestrol, formononetin and biochanin A. To study the biological activity of C. arietinum, the human osteosarcoma Saos-2 and human breast cancer MCF-7 cell lines were used. The extracts obtained from fermented sprouts exhibited the strongest ability to decrease intracellular oxidative stress in both types of cells. They augmented mineralization and alkaline phosphatase activity in Saos-2 cells, as well as diminished the secretion of interleukin-6 and tumor necrosis factor α. Simultaneously, the extracts, at the same doses, inhibited the migration of MCF-7 cells. On the other hand, elevated concentrations of C. arietinum induced apoptosis in estrogen-dependent MCF-7 cells, while lower doses stimulated cell proliferation. These results are important for carefully considering the use of fermented C. arietinum sprouts as a dietary supplement component for the prevention of osteoporosis.
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Affiliation(s)
- Małgorzata Zakłos-Szyda
- Faculty of Biotechnology and Food Sciences, Institute of Molecular and Industrial Biotechnology, Lodz University of Technology, Stefanowskiego 4/10, 90-924 Lodz, Poland
| | - Ilona Gałązka-Czarnecka
- Faculty of Biotechnology and Food Sciences, Institute of Food Technology and Analysis, Lodz University of Technology, Stefanowskiego 4/10, 90-924 Lodz, Poland; (I.G.-C.); (J.G.); (G.B.)
| | - Joanna Grzelczyk
- Faculty of Biotechnology and Food Sciences, Institute of Food Technology and Analysis, Lodz University of Technology, Stefanowskiego 4/10, 90-924 Lodz, Poland; (I.G.-C.); (J.G.); (G.B.)
| | - Grażyna Budryn
- Faculty of Biotechnology and Food Sciences, Institute of Food Technology and Analysis, Lodz University of Technology, Stefanowskiego 4/10, 90-924 Lodz, Poland; (I.G.-C.); (J.G.); (G.B.)
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13
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Food as medicine: targeting the uraemic phenotype in chronic kidney disease. Nat Rev Nephrol 2020; 17:153-171. [PMID: 32963366 DOI: 10.1038/s41581-020-00345-8] [Citation(s) in RCA: 136] [Impact Index Per Article: 27.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/10/2020] [Indexed: 02/07/2023]
Abstract
The observation that unhealthy diets (those that are low in whole grains, fruits and vegetables, and high in sugar, salt, saturated fat and ultra-processed foods) are a major risk factor for poor health outcomes has boosted interest in the concept of 'food as medicine'. This concept is especially relevant to metabolic diseases, such as chronic kidney disease (CKD), in which dietary approaches are already used to ameliorate metabolic and nutritional complications. Increased awareness that toxic uraemic metabolites originate not only from intermediary metabolism but also from gut microbial metabolism, which is directly influenced by diet, has fuelled interest in the potential of 'food as medicine' approaches in CKD beyond the current strategies of protein, sodium and phosphate restriction. Bioactive nutrients can alter the composition and metabolism of the microbiota, act as modulators of transcription factors involved in inflammation and oxidative stress, mitigate mitochondrial dysfunction, act as senolytics and impact the epigenome by altering one-carbon metabolism. As gut dysbiosis, inflammation, oxidative stress, mitochondrial dysfunction, premature ageing and epigenetic changes are common features of CKD, these findings suggest that tailored, healthy diets that include bioactive nutrients as part of the foodome could potentially be used to prevent and treat CKD and its complications.
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Agil A, Chayah M, Visiedo L, Navarro-Alarcon M, Rodríguez Ferrer JM, Tassi M, Reiter RJ, Fernández-Vázquez G. Melatonin Improves Mitochondrial Dynamics and Function in the Kidney of Zücker Diabetic Fatty Rats. J Clin Med 2020; 9:jcm9092916. [PMID: 32927647 PMCID: PMC7564180 DOI: 10.3390/jcm9092916] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 09/04/2020] [Accepted: 09/08/2020] [Indexed: 12/13/2022] Open
Abstract
Obesity and associated diabetes (diabesity) impair kidney mitochondrial dynamics by augmenting fission and diminishing fusion, which results in mitochondrial and renal dysfunction. Based on available evidence, the antioxidant activities of melatonin may improve impaired renal mitochondrial function in obese diabetic animals by restoring the imbalanced dynamics through inhibiting fission and promoting fusion. Male Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally treated either with melatonin (10 mg/kg BW/day) (M-ZDF and M-ZL) or vehicle (C-ZDF and C-ZL) for 17 weeks. Kidney function was evaluated by measurement of total urine volume, proteinuria, creatinine clearance, and assessment of kidney mitochondrial dynamics and function. C-ZDF exhibited impaired dynamics and function of kidney mitochondria in comparison to C-ZL. Melatonin improved nephropathy of ZDF rats and modulated their mitochondrial dynamics by reducing expression of Drp1 fission marker and increasing that of fusion markers, Mfn2 and Opa1. Furthermore, melatonin ameliorated mitochondrial dysfunction by increasing respiratory control index and electron transfer chain complex IV activity. In addition, it lowered mitochondrial oxidative status. Our findings show that melatonin supplementation improves nephropathy likely via modulation of the mitochondrial fission/fusion balance and function in ZDF rats.
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Affiliation(s)
- Ahmad Agil
- Department of Pharmacology and Neurosciences Institute, School of Medicine, University of Granada, 18016 Granada, Spain; (M.C.); (L.V.)
- Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospital of Granada, 18016 Granada, Spain
- Correspondence: ; Tel.: +34-625-143-359
| | - Meriem Chayah
- Department of Pharmacology and Neurosciences Institute, School of Medicine, University of Granada, 18016 Granada, Spain; (M.C.); (L.V.)
- Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospital of Granada, 18016 Granada, Spain
| | - Lucia Visiedo
- Department of Pharmacology and Neurosciences Institute, School of Medicine, University of Granada, 18016 Granada, Spain; (M.C.); (L.V.)
- Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospital of Granada, 18016 Granada, Spain
| | - Miguel Navarro-Alarcon
- Department of Nutrition and Bromatology, School of Pharmacy, University of Granada, 18071 Granada, Spain;
| | | | - Mohamed Tassi
- Service of Microscopy, CIBM, University of Granada, 18016 Granada, Spain;
| | - Russel J. Reiter
- Department of Cellular and Structural Biology, University of Texas Health Science at San Antonio, San Antonio, TX 78229, USA;
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15
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Jurado-Fasoli L, Mochon-Benguigui S, Castillo MJ, Amaro-Gahete FJ. Association between sleep quality and time with energy metabolism in sedentary adults. Sci Rep 2020; 10:4598. [PMID: 32165704 PMCID: PMC7067839 DOI: 10.1038/s41598-020-61493-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 02/25/2020] [Indexed: 01/24/2023] Open
Abstract
The aim of the present study was to investigate the relationship of sleep quality and time with basal metabolic rate (BMR) and fuel oxidation in basal conditions and during exercise in sedentary middle-aged adults. We also studied the mediation role of dietary intake and adherence to the traditional Mediterranean Diet in the relationship between sleep parameters and energy metabolism parameters.A secondary analysis of the FIT-AGEING study was undertaken. 70 middle-aged sedentary adults (40-65 years old) participated in the present study. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and wrist accelerometers (ActiSleep, Actigraph, Pensacola, Florida, USA) for 7 consecutive days. BMR was measured with indirect calorimetry and fuel oxidation was estimated through stoichiometric equations. Maximal fat oxidation was determined by a walking graded exercise test and dietary intake with 24 h recalls. Adherence to the traditional Mediterranean diet was assessed through the PREDIMED questionnaire. PSQI global score (poor sleep quality) was associated with lower basal fat oxidation (BFox), both expressed in g/min and as a percentage of BMR, independently of confounders. We did not find any association between other sleep and energy metabolism parameters. No mediating role of the dietary intake or PREDIMED global score was observed in the association of PSQI and BFox. In conclusion, our study showed that a subjective poor sleep quality was associated with lower BFox, which is not mediated by dietary intake in sedentary adults.
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Affiliation(s)
- Lucas Jurado-Fasoli
- Department of Medical Physiology, School of Medicine, University of Granada, 18016, Granada, Spain.
- PROmoting FITness and Health through physical activity research group (PROFITH), Department of Physical Education and Sports, Faculty of Sport Sciences, University of Granada, Granada, Spain.
| | - Sol Mochon-Benguigui
- Department of Medical Physiology, School of Medicine, University of Granada, 18016, Granada, Spain
| | - Manuel J Castillo
- Department of Medical Physiology, School of Medicine, University of Granada, 18016, Granada, Spain
| | - Francisco J Amaro-Gahete
- Department of Medical Physiology, School of Medicine, University of Granada, 18016, Granada, Spain.
- PROmoting FITness and Health through physical activity research group (PROFITH), Department of Physical Education and Sports, Faculty of Sport Sciences, University of Granada, Granada, Spain.
- Camilo José Cela University, Madrid, Spain.
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16
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Ferro Y, Montalcini T, Mazza E, Foti D, Angotti E, Gliozzi M, Nucera S, Paone S, Bombardelli E, Aversa I, Musolino V, Mollace V, Pujia A. Randomized Clinical Trial: Bergamot Citrus and Wild Cardoon Reduce Liver Steatosis and Body Weight in Non-diabetic Individuals Aged Over 50 Years. Front Endocrinol (Lausanne) 2020; 11:494. [PMID: 32849284 PMCID: PMC7431622 DOI: 10.3389/fendo.2020.00494] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 06/22/2020] [Indexed: 12/16/2022] Open
Abstract
Background: Non-alcoholic fatty liver disease is the most common cause of liver-related morbidity and mortality in the world. However, no effective pharmacological treatment for this condition has been found. Purpose: This study evaluated the effect of a nutraceutical containing bioactive components from Bergamot citrus and wild cardoon as a treatment for individuals with fatty liver disease. The primary outcome measure was the change in liver fat content. Methods: A total of 102 patients with liver steatosis were enrolled in a double-blind placebo controlled clinical trial. The intervention group received a nutraceutical containing a Bergamot polyphenol fraction and Cynara Cardunculus extract, 300 mg/day for 12 weeks. The control group received a placebo daily. Liver fat content, by transient elastography, serum transaminases, lipids and glucose were measured at the baseline and the end of the study. Results: We found a greater liver fat content reduction in the participants taking the nutraceutical rather than placebo (-48.2 ± 39 vs. -26.9 ± 43 dB/m, p = 0.02); The percentage CAP score reduction was statistically significant in those with android obesity, overweight/obesity as well as in women. However, after adjustment for weight change, the percentage CAP score reduction was statistically significant only in those over 50 years (44 vs. 78% in placebo and nutraceutical, respectively, p = 0.007). Conclusions: This specific nutraceutical containing bioactive components from Bergamot and wild cardoon reduced the liver fat content during 12 weeks in individuals with liver steatosis over 50 years. If confirmed, this nutraceutical could become the cornerstone treatment of patients affected by liver steatosis. Clinical Trial Registration: www.isrctn.com, identifier ISRCTN12833814.
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Affiliation(s)
- Yvelise Ferro
- Department of Health Science, University Magna Grecia, Catanzaro, Italy
| | - Tiziana Montalcini
- Department of Clinical and Experimental Medicine, University Magna Grecia, Catanzaro, Italy
- *Correspondence: Tiziana Montalcini
| | - Elisa Mazza
- Department of Medical and Surgical Science, University Magna Grecia, Catanzaro, Italy
| | - Daniela Foti
- Department of Health Science, University Magna Grecia, Catanzaro, Italy
| | - Elvira Angotti
- Department of Clinical and Experimental Medicine, University Magna Grecia, Catanzaro, Italy
| | - Micaela Gliozzi
- Department of Health Science, University Magna Grecia, Catanzaro, Italy
| | - Saverio Nucera
- Department of Health Science, University Magna Grecia, Catanzaro, Italy
| | - Sara Paone
- Department of Health Science, University Magna Grecia, Catanzaro, Italy
| | | | - Ilaria Aversa
- Department of Clinical and Experimental Medicine, University Magna Grecia, Catanzaro, Italy
| | - Vincenzo Musolino
- Department of Health Science, University Magna Grecia, Catanzaro, Italy
| | - Vincenzo Mollace
- Department of Health Science, University Magna Grecia, Catanzaro, Italy
| | - Arturo Pujia
- Department of Medical and Surgical Science, University Magna Grecia, Catanzaro, Italy
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Sheik Abdul N, Nagiah S, Chuturgoon AA. The neglected foodborne mycotoxin Fusaric acid induces bioenergetic adaptations by switching energy metabolism from mitochondrial processes to glycolysis in a human liver (HepG2) cell line. Toxicol Lett 2020; 318:74-85. [DOI: 10.1016/j.toxlet.2019.10.013] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Revised: 10/03/2019] [Accepted: 10/17/2019] [Indexed: 12/21/2022]
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Cassanye A, Martín-Gari M, Portero-Otin M, Serrano JCE. Adipose Tissue Mitochondrial Factors Profile after Dietary Bioactive Compound Weight Reduction Treatments in a Mice Obesity Model. Int J Mol Sci 2019; 20:E5870. [PMID: 31771102 PMCID: PMC6928597 DOI: 10.3390/ijms20235870] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 11/14/2019] [Accepted: 11/19/2019] [Indexed: 01/02/2023] Open
Abstract
Prolonged caloric intake above energy needs disturbs the body's ability to store and manage the excess of energy intake, leading to the onset of chronic degenerative diseases. This study aimed to compare the effect of three foods, which contain demonstrated bioactive compounds in the treatment of obesity and as an adjuvant in obesity energy restriction treatments. In a mice obesity model induced through a high-fat diet; fish oil, soluble fibre, and soy were incorporated to evaluate its capacity to modulate metabolic factors in adipose tissue during a continued fat intake or weight reduction through a normocaloric diet. As a result, fish oil improved mitochondrial related, adipose tissue hormone expression, and oxidation products when high-fat diets are consumed; while soluble fibre improved glucose and inflammation pathways during high-fat diet intake. In weight reduction treatments few differential features, as a treatment adjuvant, were observed for fish oil and soy; while soluble fibre was able to improve the weight reduction effects induced by a normocaloric diet. As a conclusion, soluble fibre supplementation compared to an energy reduction program, was the only treatment able to induce a significant additional effect in the improvement of weight loss and adipose tissue metabolism.
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Affiliation(s)
| | | | | | - José CE Serrano
- Department of Experimental Medicine, NUTREN-Nutrigenomics, University of Lleida, 25198 Lleida, Spain; (A.C.); (M.M.-G.); (M.P.-O.)
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Nikbakht F, Khadem Y, Haghani S, Hoseininia H, Moein Sadat A, Heshemi P, Jamali N. Protective Role of Apigenin Against Aβ 25-35 Toxicity Via Inhibition of Mitochondrial Cytochrome c Release. Basic Clin Neurosci 2019; 10:557-566. [PMID: 32477473 PMCID: PMC7253805 DOI: 10.32598/bcn.9.10.385] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 09/10/2018] [Accepted: 12/29/2018] [Indexed: 01/06/2023] Open
Abstract
Introduction: Cognitive dysfunction is the most common problem of patients with Alzheimer Disease (AD). The pathological mechanism of cognitive impairment in AD may contribute to neuronal loss, synaptic dysfunction, and alteration in neurotransmitters receptors. Mitochondrial synapses dysfunction due to the accumulation of Amyloid Beta (Aβ) is one of the earliest pathological features of AD. The flavone apigenin has been reported to play some protective roles in AD through the anti-oxidative and anti-inflammatory properties. This study aimed at investigating the effects of apigenin on spatial working memory and neural protection by restoring mitochondrial dysfunction and inhibition of caspase 9. Methods: Intracerebroventricular (ICV) microinjection of Aβ 25–35 was used for AD modeling. Working memory was assessed 21 days later using the Y maze test. Neuronal loss was detected in the hilar area of the hippocampus using Nissl and Fluoro-jade B staining, whereas immunohistochemistry was used to illustrate cytochrome c positive cells and caspase 9. Results: The results revealed that apigenin significantly ameliorated spatial working memory. It also significantly reduced the number of degenerative neurons in the hilus area. Apigenin almost completely blocked the release of cytochrome c and caspase 9 in hilus. Conclusion: Apigenin may improve the spatial working memory deficits and neuronal degeneration through the amelioration of the mitochondrial dysfunction.
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Affiliation(s)
- Farnaz Nikbakht
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Yasaman Khadem
- Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Sobhan Haghani
- Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hadiseh Hoseininia
- Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Alireza Moein Sadat
- Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Paria Heshemi
- Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Nida Jamali
- Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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Castora FJ. Mitochondrial function and abnormalities implicated in the pathogenesis of ASD. Prog Neuropsychopharmacol Biol Psychiatry 2019; 92:83-108. [PMID: 30599156 DOI: 10.1016/j.pnpbp.2018.12.015] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Revised: 12/20/2018] [Accepted: 12/24/2018] [Indexed: 12/18/2022]
Abstract
Mitochondria are the powerhouse that generate over 90% of the ATP produced in cells. In addition to its role in energy production, the mitochondrion also plays a major role in carbohydrate, fatty acid, amino acid and nucleotide metabolism, programmed cell death (apoptosis), generation of and protection against reactive oxygen species (ROS), immune response, regulation of intracellular calcium ion levels and even maintenance of gut microbiota. With its essential role in bio-energetic as well as non-energetic biological processes, it is not surprising that proper cellular, tissue and organ function is dependent upon proper mitochondrial function. Accordingly, mitochondrial dysfunction has been shown to be directly linked to a variety of medical disorders, particularly neuromuscular disorders and increasing evidence has linked mitochondrial dysfunction to neurodegenerative and neurodevelopmental disorders such as Alzheimer's Disease (AD), Parkinson's Disease (PD), Rett Syndrome (RS) and Autism Spectrum Disorders (ASD). Over the last 40 years there has been a dramatic increase in the diagnosis of ASD and, more recently, an increasing body of evidence indicates that mitochondrial dysfunction plays an important role in ASD development. In this review, the latest evidence linking mitochondrial dysfunction and abnormalities in mitochondrial DNA (mtDNA) to the pathogenesis of autism will be presented. This review will also summarize the results of several recent `approaches used for improving mitochondrial function that may lead to new therapeutic approaches to managing and/or treating ASD.
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Affiliation(s)
- Frank J Castora
- Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA, USA; Department of Neurology, Eastern Virginia Medical School, Norfolk, VA, USA.
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21
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Teixeira LDL, Dörr F, Dias CT, Pinto E, Lajolo FM, Villas-Bôas SG, Hassimotto NM. Human urine metabolomic signature after ingestion of polyphenol-rich juice of purple grumixama (Eugenia brasiliensis Lam.). Food Res Int 2019; 120:544-552. [DOI: 10.1016/j.foodres.2018.11.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Revised: 10/26/2018] [Accepted: 11/02/2018] [Indexed: 02/07/2023]
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22
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Sergi D, Naumovski N, Heilbronn LK, Abeywardena M, O'Callaghan N, Lionetti L, Luscombe-Marsh N. Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet. Front Physiol 2019; 10:532. [PMID: 31130874 PMCID: PMC6510277 DOI: 10.3389/fphys.2019.00532] [Citation(s) in RCA: 215] [Impact Index Per Article: 35.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Accepted: 04/15/2019] [Indexed: 12/17/2022] Open
Abstract
Mitochondrial dysfunction has been implicated in the pathogenesis of insulin resistance, the hallmark of type 2 diabetes mellitus (T2DM). However, the cause-effect relationship remains to be fully elucidated. Compelling evidence suggests that boosting mitochondrial function may represent a valuable therapeutic tool to improve insulin sensitivity. Mitochondria are highly dynamic organelles, which adapt to short- and long-term metabolic perturbations by undergoing fusion and fission cycles, spatial rearrangement of the electron transport chain complexes into supercomplexes and biogenesis governed by peroxisome proliferator-activated receptor γ co-activator 1α (PGC 1α). However, these processes appear to be dysregulated in type 2 diabetic individuals. Herein, we describe the mechanistic link between mitochondrial dysfunction and insulin resistance in skeletal muscle alongside the intracellular pathways orchestrating mitochondrial bioenergetics. We then review current evidence on nutritional tools, including fatty acids, amino acids, caloric restriction and food bioactive derivatives, which may enhance insulin sensitivity by therapeutically targeting mitochondrial function and biogenesis.
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Affiliation(s)
- Domenico Sergi
- Nutrition and Health Substantiation Group, Nutrition and Health Program, Health and Biosecurity, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Adelaide, SA, Australia.,Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
| | - Nenad Naumovski
- Faculty of Health, University of Canberra, Canberra, ACT, Australia.,Collaborative Research in Bioactives and Biomarkers (CRIBB) Group, Canberra, ACT, Australia
| | | | - Mahinda Abeywardena
- Nutrition and Health Substantiation Group, Nutrition and Health Program, Health and Biosecurity, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Adelaide, SA, Australia
| | - Nathan O'Callaghan
- Nutrition and Health Substantiation Group, Nutrition and Health Program, Health and Biosecurity, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Adelaide, SA, Australia
| | - Lillà Lionetti
- Department of Chemistry and Biology "A. Zambelli", University of Salerno, Fisciano, Italy
| | - Natalie Luscombe-Marsh
- Nutrition and Health Substantiation Group, Nutrition and Health Program, Health and Biosecurity, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Adelaide, SA, Australia.,Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
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23
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Rebollo-Hernanz M, Zhang Q, Aguilera Y, Martín-Cabrejas MA, de Mejia EG. Cocoa Shell Aqueous Phenolic Extract Preserves Mitochondrial Function and Insulin Sensitivity by Attenuating Inflammation between Macrophages and Adipocytes In Vitro. Mol Nutr Food Res 2019; 63:e1801413. [PMID: 31018035 DOI: 10.1002/mnfr.201801413] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2018] [Revised: 03/10/2019] [Indexed: 12/12/2022]
Abstract
SCOPE The aim is to assess the action of an aqueous extract from cocoa shell (CAE) and its main phenolic compounds to prevent the loss of obesity-induced mitochondrial function and insulin sensitivity, targeting inflammation between macrophages-adipocytes in vitro. METHODS AND RESULTS CAE (31-500 µg mL-1 ) inhibits 3T3-L1 adipocytes lipid accumulation and induces browning during differentiation. LPS-stimulated RAW264.7 macrophages show reduced inducible nitric oxide synthase and cyclooxygenase-2 expression and lowered pro-inflammatory cytokine production when treated with CAE and pure phenolics. Inflammatory crosstalk created by stimulating adipocytes with macrophage-conditioned media (CM) is arrested; CAE diminishes tumor necrosis factor-α (67%) and promotes adiponectin secretion (12.3-fold). Mitochondrial function, measured by reactive oxygen species production, mitochondrial content, and activity, is preserved in CM-treated adipocytes through up-regulating peroxisome proliferator-activated receptor gamma coactivator 1-α expression. Increases in insulin receptor (9-fold), phosphoinositide 3-kinase (3-fold), protein kinase B (4-fold) phosphorylation, and a decrease in insulin receptor substrate 1 serine phosphorylation induce increased glucose uptake (34%) and glucose transporter 4 translocation (14-fold) in CM-induced adipocytes. CONCLUSION CAE phenolics promote a beige phenotype in adipocytes. Macrophages-adipocytes inflammatory interaction is reduced preventing mitochondrial dysfunction and insulin resistance. For the first time, CAE shows a positive effect on adipogenesis and inflammation-related disorders.
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Affiliation(s)
- Miguel Rebollo-Hernanz
- Institute of Food Science Research, CIAL (UAM-CSIC), 28049, Madrid, Spain.,Department of Agricultural Chemistry and Food Science, Universidad Autónoma de Madrid, 28049, Madrid, Spain.,Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, IL, 61801, USA
| | - Qiaozhi Zhang
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, IL, 61801, USA.,College of Food Science, Northeast Agricultural University, Harbin, 150030, China
| | - Yolanda Aguilera
- Institute of Food Science Research, CIAL (UAM-CSIC), 28049, Madrid, Spain.,Department of Agricultural Chemistry and Food Science, Universidad Autónoma de Madrid, 28049, Madrid, Spain
| | - Maria A Martín-Cabrejas
- Institute of Food Science Research, CIAL (UAM-CSIC), 28049, Madrid, Spain.,Department of Agricultural Chemistry and Food Science, Universidad Autónoma de Madrid, 28049, Madrid, Spain
| | - Elvira Gonzalez de Mejia
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, IL, 61801, USA
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24
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Sarr O, Mathers KE, Zhao L, Dunlop K, Chiu J, Guglielmo CG, Bureau Y, Cheung A, Raha S, Lee TY, Regnault TRH. Western diet consumption through early life induces microvesicular hepatic steatosis in association with an altered metabolome in low birth weight Guinea pigs. J Nutr Biochem 2019; 67:219-233. [PMID: 30981986 DOI: 10.1016/j.jnutbio.2019.02.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Revised: 02/20/2019] [Accepted: 02/28/2019] [Indexed: 02/07/2023]
Abstract
Uteroplacental insufficiency-induced low birth weight (LBW) and postnatal high saturated fat/high sucrose-fructose diet (Western Diet, WD) consumption have been independently associated with the development of hepatic steatosis, while their additive effect on fatty acid, acylcarnitine and amino acid profiles in early adulthood have not been widely reported. We employed LBW, generated via uterine artery ablation, and normal birth weight (NBW) male guinea pigs fed either a WD or control diet (CD) from weaning to postnatal day 150 (early adulthood). Hepatic steatosis was absent in CD-fed offspring, while NBW/WD offspring displayed macrovesicular steatosis and LBW/WD offspring exhibited microvesicular steatosis, both occurring in a lean phenotype. Life-long consumption of the WD, irrespective of birth weight, was associated with an increase in hepatic medium- and long-chain saturated fatty acids, monounsaturated fatty acids, acylcarnitines, reduced oxidative phosphorylation complex III activity and polyunsaturated fatty acids, and molecular evidence of disrupted hepatic insulin signaling. In NBW/WD, hepatic C15:1 and C16:1n-6 fatty acids in phospholipids, C16, C18 and C18:1 acylcarnitines, concentrations of aspartate, phenylalanine, tyrosine and tryptophan and expression of carnitine palmitoyltransferase 1 alpha (CPT1α) and uncoupling protein 2 (UCP2) genes were elevated compared to LBW/WD livers. Our results suggest that LBW and life-long WD combined are influential in promoting hepatic microvesicular steatosis in conjunction with a specific mitochondrial gene expression and metabolomic profile in early adulthood.
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Affiliation(s)
- Ousseynou Sarr
- Department of Obstetrics and Gynaecology, Western University, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada; Children's Health Research Institute, London, Ontario, Canada
| | | | - Lin Zhao
- Department of Obstetrics and Gynaecology, Western University, London, Ontario, Canada
| | - Kristyn Dunlop
- Department of Physiology and Pharmacology, Western University
| | - Jacky Chiu
- Department of Physiology and Pharmacology, Western University
| | | | - Yves Bureau
- Department of Medical Biophysics, Western University
| | - Anson Cheung
- Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada
| | - Sandeep Raha
- Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada
| | - Ting-Yim Lee
- Lawson Health Research Institute, London, Ontario, Canada; Departments of Medical Imaging, Medical Biophysics, and Oncology, Western University; Robarts Research Institute, London, Ontario, Canada
| | - Timothy R H Regnault
- Department of Obstetrics and Gynaecology, Western University, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada; Children's Health Research Institute, London, Ontario, Canada; Department of Physiology and Pharmacology, Western University.
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25
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Baruah TJ, Kma L. Vicenin-2 acts as a radiosensitizer of the non-small cell lung cancer by lowering Akt expression. Biofactors 2019; 45:200-210. [PMID: 30496626 DOI: 10.1002/biof.1472] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Revised: 09/28/2018] [Accepted: 10/04/2018] [Indexed: 12/27/2022]
Abstract
Non-small cell lung cancer (NSCLC) has a very high rate of incidence and is resistant to chemo- and radiotherapy. Vicenin-2 (VCN-2) is a flavonoid obtained from Ocimum sanctum L. and it has been reported to have radioprotective, anticancer, and radiosensitizing properties. We have conducted this study to check the effect of VCN-2 on the cell viability and the effect on PTEN (Phosphatase and tensin homolog), PI3KCA (Phosphatidylinositol 4, 5-biphosphate 3-kinase catalytic subunit alpha isoform/PI3K 110α subunit), and Akt1 when VCN-2 was used alone and in combination with radiation in the NSCLC cell line NCI-H23 (H23). We have also checked the effect of VCN-2 on various pro- and anti-apoptotic genes and the ultra-morphological changes that occurred in the cells when VCN-2 is used alone and in combination with radiation. VCN-2 was able to lower cancer cell survival and phosphorylated Akt while promoting the expression of pro-apoptotic genes and down-regulating anti-apoptotic genes. We also observed the apoptosis-associated ultra-morphological changes in the VCN-2-treated cells. Our study have demonstrated that VCN-2 can be a potential chemotherapeutic and radiosensitizing agent in NSCLC. © 2018 BioFactors, 45(2):200-210, 2019.
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Affiliation(s)
- Taranga Jyoti Baruah
- Cancer and Radiation Countermeasures Unit, Department of Biochemistry, North-Eastern Hill University, Shillong, India
| | - Lakhon Kma
- Cancer and Radiation Countermeasures Unit, Department of Biochemistry, North-Eastern Hill University, Shillong, India
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26
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Mafra D, Gidlund EK, Borges NA, Magliano DC, Lindholm B, Stenvinkel P, von Walden F. Bioactive food and exercise in chronic kidney disease: Targeting the mitochondria. Eur J Clin Invest 2018; 48:e13020. [PMID: 30144313 DOI: 10.1111/eci.13020] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2017] [Revised: 08/11/2018] [Accepted: 08/22/2018] [Indexed: 12/16/2022]
Abstract
Chronic kidney disease (CKD), which affects 10%-15% of the population, associates with a range of complications-such as cardiovascular disease, frailty, infections, muscle and bone disorders and premature ageing-that could be related to alterations of mitochondrial number, distribution, structure and function. As mitochondrial biogenesis, bioenergetics and the dynamic mitochondrial networks directly or indirectly regulate numerous intra- and extracellular functions, the mitochondria have emerged as an important target for interventions aiming at preventing or improving the treatment of complications in CKD. In this review, we discuss the possible role of bioactive food compounds and exercise in the modulation of the disturbed mitochondrial function in a uraemic milieu.
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Affiliation(s)
- Denise Mafra
- Graduate Program in Medical Sciences, Fluminense Federal University (UFF), Niterói, Rio de Janeiro, Brazil.,Graduate Program in Cardiovascular Sciences, Fluminense Federal University (UFF), Niterói, Rio de Janeiro, Brazil
| | - Eva-Karin Gidlund
- Division of Molecular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | - Natália Alvarenga Borges
- Graduate Program in Cardiovascular Sciences, Fluminense Federal University (UFF), Niterói, Rio de Janeiro, Brazil
| | - D'Angelo Carlo Magliano
- Graduate Program in Cardiovascular Sciences, Fluminense Federal University (UFF), Niterói, Rio de Janeiro, Brazil
| | - Bengt Lindholm
- Division of Renal Medicine, Department of Clinical Science Intervention and Technology, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Peter Stenvinkel
- Division of Renal Medicine, Department of Clinical Science Intervention and Technology, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Ferdinand von Walden
- Division of Pediatric Neurology, Department of Women's and Children's health, Karolinska Institutet, Stockholm, Sweden
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27
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Liu P, Lin H, Xu Y, Zhou F, Wang J, Liu J, Zhu X, Guo X, Tang Y, Yao P. Frataxin-Mediated PINK1-Parkin-Dependent Mitophagy in Hepatic Steatosis: The Protective Effects of Quercetin. Mol Nutr Food Res 2018; 62:e1800164. [PMID: 29935106 DOI: 10.1002/mnfr.201800164] [Citation(s) in RCA: 80] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2018] [Revised: 05/20/2018] [Indexed: 12/18/2022]
Abstract
SCOPE Naturally occurring quercetin has been found to induce mitophagy and prevent nonalcoholic fatty liver disease (NAFLD). However, it still remains elusive whether frataxin upregulation by quercetin contributes to the beneficial effect through mitophagy or not. METHODS AND RESULTS Adult male C57BL/J mice were fed a high-fat diet (HFD, 60% of energy from fat) with quercetin (100 mg kg-1 body weight) or not for 10 weeks. Quercetin alleviated HFD-induced histopathological changes, disorders of lipid metabolism, and mitochondrial damage. Moreover, quercetin blocked mitophagy suppression by HFD based on the increased LC3II, PTEN-induced putative kinase 1 (PINK1) and Beclin1 expressions, as well as decreased p62 levels. Quercetin also improved the Parkin translocation to mitochondria confirmed by immunofluorescence. Specifically, frataxin was lowered in the liver of HFD-fed mice or HepG2 cell incubated with oleate/palmitate but restored by quercetin, and quercetin's regulation of frataxin may depend on p53. Furthermore, lentivirus-mediated stable knockdown of frataxin in HepG2 inhibited PINK1-Parkin-associated mitophagy and resulted in lipid accumulation. Frataxin was further decreased by free fatty acids in knockdown cells concomitantly with depressed PINK1-Parkin-associated mitophagy, which was partially normalized by quercetin. CONCLUSION Quercetin alleviated hepatic steatosis by enhancing frataxin-mediated PINK1/Parkin-dependent mitophagy, highlighting a promising preventive strategy and mechanism for NAFLD by quercetin.
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Affiliation(s)
- Peiyi Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, 430030, Hubei, China
| | - Hongkun Lin
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, 430030, Hubei, China
| | - Yanyan Xu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, 430030, Hubei, China
| | - Feng Zhou
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, 430030, Hubei, China
| | - Jing Wang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, 430030, Hubei, China
| | - Jingjing Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, 430030, Hubei, China
| | - Xinhong Zhu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, 430030, Hubei, China
| | - Xiaoping Guo
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, 430030, Hubei, China
| | - Yuhan Tang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, 430030, Hubei, China
| | - Ping Yao
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, 430030, Hubei, China
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28
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Dos Santos TW, Miranda J, Teixeira L, Aiastui A, Matheu A, Gambero A, Portillo MP, Ribeiro ML. Yerba Mate Stimulates Mitochondrial Biogenesis and Thermogenesis in High-Fat-Diet-Induced Obese Mice. Mol Nutr Food Res 2018; 62:e1800142. [PMID: 29851217 DOI: 10.1002/mnfr.201800142] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Revised: 05/07/2018] [Indexed: 01/24/2023]
Abstract
SCOPE The potential effects of yerba mate (YM) on mitochondrial biogenesis and thermogenesis are evaluated. METHODS AND RESULTS The in vitro effects of YM on mitochondrial respiration are assessed in C2C12 cells. The expression of genes related to mitochondrial biogenesis and thermogenesis are analyzed by quantitative PCR. The in vivo experiments are performed on mice fed a high-fat diet (HFD) and treated with YM extract. Indirect calorimetry was performed, and the expression of genes and proteins related to mitochondrial biogenesis, thermogenesis, and de novo lipogenesis is determined by quantitative PCR and western blot. Our in vitro data indicate that YM increases mtDNA copy number as well as mitochondrial spare respiratory capacity and coupling efficiency. The gene expression profile reinforces this evidence, indicating a modulation of genes downstream of Ampk. In vivo, it is found that YM partially prevents diet-induced obesity by increasing energy expenditure and enhancing mitochondrial biogenesis via the AMPK/SIRT1/PGC1α pathway. CONCLUSIONS YM stimulates mitochondriogenesis and Ucp expression, leading to an increase in the spare respiratory capacity and energy dissipation. These effects may help to better understand the potential use of YM for obesity treatment.
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Affiliation(s)
- Tanila Wood Dos Santos
- Unidade Integrada de Farmacologia e Gastroenterologia, Universidade São Francisco, Bragança Paulista, São Paulo, 12916-900, Brazil.,Programa de Pos Graduação em Genetica e Biologia Molecular, State University of Campinas,, Campinas, São Paulo, 13083-862, Brazil
| | - Jonatan Miranda
- Nutrition and Obesity Group, Department of Nutrition and Food Science, University of the Basque Country (UPV/EHU) and Lucio Lascaray Research Institute, Vitoria, 01080, Spain.,CIBERobn Physiopathology of Obesity and Nutrition, Instituto de Salud Carlos III (ISCIII), 28029, Spain
| | - Lucimara Teixeira
- Unidade Integrada de Farmacologia e Gastroenterologia, Universidade São Francisco, Bragança Paulista, São Paulo, 12916-900, Brazil
| | - Ana Aiastui
- Neuroscience Area, Biodonostia Health Research Institute, San Sebastian, 20014, Spain
| | - Ander Matheu
- Neuroscience Area, Biodonostia Health Research Institute, San Sebastian, 20014, Spain
| | - Alessandra Gambero
- Unidade Integrada de Farmacologia e Gastroenterologia, Universidade São Francisco, Bragança Paulista, São Paulo, 12916-900, Brazil
| | - María P Portillo
- Nutrition and Obesity Group, Department of Nutrition and Food Science, University of the Basque Country (UPV/EHU) and Lucio Lascaray Research Institute, Vitoria, 01080, Spain.,CIBERobn Physiopathology of Obesity and Nutrition, Instituto de Salud Carlos III (ISCIII), 28029, Spain
| | - Marcelo Lima Ribeiro
- Unidade Integrada de Farmacologia e Gastroenterologia, Universidade São Francisco, Bragança Paulista, São Paulo, 12916-900, Brazil
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29
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Rao C, Agarwal N, Alauddin, Chaturvedi S, Azmi L, Shukla I, Naseem Z. Gastroprotective effect of formononetin against ethanol-induced gastric ulceration in rats via augmentation of cytoprotective markers and curtailing apoptotic gene expression. Pharmacogn Mag 2018. [DOI: 10.4103/pm.pm_205_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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30
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Eya JC, Yossa R, Perera D, Okubajo O, Gannam A. Combined effects of diets and temperature on mitochondrial function, growth and nutrient efficiency in rainbow trout (Oncorhynchus mykiss). Comp Biochem Physiol B Biochem Mol Biol 2017; 212:1-11. [PMID: 28687361 DOI: 10.1016/j.cbpb.2017.06.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Revised: 06/21/2017] [Accepted: 06/26/2017] [Indexed: 10/19/2022]
Abstract
A 4×3 factorial experiment was conducted to evaluate the effects of two dietary protein sources (mixed fishmeal/plant protein-, and plant protein- based diet), two dietary lipid levels (10% and 20%) and three water temperatures (10°C, 14°C, and 18°C) on the growth performance, nutrient utilization efficiencies and mitochondrial enzyme complex activities in rainbow trout Oncorhynchus mykiss (average weight±SD, 39.5±5g) over a 180day rearing period. At the end of the experiment, weight gain (WG), condition factor (CF), and feed efficiency (FE) were significantly affected by diet×temperature interaction (P<0.05). Specific growth rate (SGR) was significantly affected by increasing temperature (P<0.05). The plant protein-based diets led to a higher CF than the mixed fishmeal/plant protein-based diets. The protein productive value (PPV), protein efficiency ratio (PER), lipid efficiency ratio, (LER) and lipid productive value (LPV) were all significantly affected by diet×temperature interaction (P<0.05). The diet×temperature interaction also had significant effects on mitochondrial enzyme complexes II, V and citrate synthase in the liver, complexes II and IV in the intestine, and complex IV in the muscle (P<0.05). Temperature had a significant main effect on the activity of the enzymatic complexes I and III in the liver, complex III and citrate synthase in the intestine, and complexes I, II, III, V and citrate synthase in the muscle (P<0.05). Diet had a significant main effect on complexes I and III in the liver, complexes II and III for the intestine and complexes I and II in the muscle (P<0.05). The significant temperature x diet interaction observed has practical ecological implications explicitly demonstrating how changes in temperature regimens as anticipated in the rising global temperature can influence organismal performance in relation to changes in dietary formulations (replacing fishmeal based diet with plant protein based ingredients). To illustrate the practical application of the observations from this study, the most economical and cost effective way to produce rainbow trout would be to use 40/10PP diet at 14°C because fish fed this treatment had a weight gain comparable to that of the fish fed the more expensive experimental diets (40/10 FM/PP, 40/20 FM/PP, and 40/20 PP).
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Affiliation(s)
- Jonathan C Eya
- Department of Biology/Gus R. Douglass Institute, West Virginia State University, Institute, WV 25112, USA.
| | - Rodrigue Yossa
- Coastal Zones Research Institute, 232B avenue de l'Église, Shippagan, N.B. E8S 1J2, Canada.
| | - Dayan Perera
- Department of Biology/Gus R. Douglass Institute, West Virginia State University, Institute, WV 25112, USA
| | - Olasupo Okubajo
- Department of Biology/Gus R. Douglass Institute, West Virginia State University, Institute, WV 25112, USA
| | - Ann Gannam
- USFWS, Abernathy Fish Technology Center, Longview, WA 98632, USA.
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31
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Jayanthy G, Roshana Devi V, Ilango K, Subramanian SP. Rosmarinic Acid Mediates Mitochondrial Biogenesis in Insulin Resistant Skeletal Muscle Through Activation of AMPK. J Cell Biochem 2017; 118:1839-1848. [PMID: 28059465 DOI: 10.1002/jcb.25869] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2016] [Accepted: 01/04/2017] [Indexed: 01/03/2023]
Abstract
Rosmarinic acid (RA), a polyphenol, is known to improve hepatic insulin sensitivity in experimental type 2 diabetes. However, its effect on skeletal muscle insulin resistance is meagerly understood. The present study was aimed to investigate the up- and downstream mediators of the molecular targets of RA in attenuating insulin resistance in the skeletal muscle both in vivo and in vitro. We found that supplementation of RA increased the expression of key genes involved in the mitochondrial biogenesis like PGC-1α, SIRT-1, and TFAM via activation of AMPK in the skeletal muscle of insulin resistant rats as well as in L6 myotubes. Further, RA treatment increased the glucose uptake and decreased the phosphorylation of serine IRS-1 while increasing the translocation of GLUT 4. Together, our findings evidenced that RA treatment significantly inhibit insulin resistance in skeletal muscle cells by enhancing mitochondrial biogenesis. J. Cell. Biochem. 118: 1839-1848, 2017. © 2017 Wiley Periodicals, Inc.
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Affiliation(s)
- Govindaraj Jayanthy
- Division of Molecular Biology, Interdisciplinary Institute of Indian System of Medicine, SRM University, Kattankulathur, Kancheepuram 603203, Tamil Nadu, India
| | - Vellai Roshana Devi
- Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, Tamil Nadu, India
| | - Kaliappan Ilango
- Division of Molecular Biology, Interdisciplinary Institute of Indian System of Medicine, SRM University, Kattankulathur, Kancheepuram 603203, Tamil Nadu, India
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32
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Ferramosca A, Di Giacomo M, Zara V. Antioxidant dietary approach in treatment of fatty liver: New insights and updates. World J Gastroenterol 2017; 23:4146-4157. [PMID: 28694655 PMCID: PMC5483489 DOI: 10.3748/wjg.v23.i23.4146] [Citation(s) in RCA: 121] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Revised: 02/22/2017] [Accepted: 06/01/2017] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common clinicopathological condition, encompassing a range of conditions caused by lipid deposition within liver cells. To date, no approved drugs are available for the treatment of NAFLD, despite the fact that it represents a serious and growing clinical problem in the Western world. Identification of the molecular mechanisms leading to NAFLD-related fat accumulation, mitochondrial dysfunction and oxidative balance impairment facilitates the development of specific interventions aimed at preventing the progression of hepatic steatosis. In this review, we focus our attention on the role of dysfunctions in mitochondrial bioenergetics in the pathogenesis of fatty liver. Major data from the literature about the mitochondrial targeting of some antioxidant molecules as a potential treatment for hepatic steatosis are described and critically analysed. There is ample evidence of the positive effects of several classes of antioxidants, such as polyphenols (i.e., resveratrol, quercetin, coumestrol, anthocyanins, epigallocatechin gallate and curcumin), carotenoids (i.e., lycopene, astaxanthin and fucoxanthin) and glucosinolates (i.e., glucoraphanin, sulforaphane, sinigrin and allyl-isothiocyanate), on the reversion of fatty liver. Although the mechanism of action is not yet fully elucidated, in some cases an indirect interaction with mitochondrial metabolism is expected. We believe that such knowledge will eventually translate into the development of novel therapeutic approaches for fatty liver.
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