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1
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Pak YK, Im S, Choi HS, Lind L, Lind M, Lee HK. Correlation between environmental pollutant exposure and cardiopulmonary health by serum biomarker analysis in the Swedish elderly population. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2025; 35:1156-1169. [PMID: 39037202 DOI: 10.1080/09603123.2024.2382306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 07/16/2024] [Indexed: 07/23/2024]
Abstract
Persistent organic pollutants (POPs) affect human health through the aryl hydrocarbon receptor (AhR) pathway and are implicated in mitochondrial dysfunction. Using data from the PIVUS study, we investigated the associations of serum AhR ligand (POP)-mediated luciferase activity (AhRL), mitochondrial ATP production inhibiting substances (MIS-ATP), and those affecting reactive oxygen species (MIS-ROS) with several metabolic syndrome (MetS) and cardiopulmonary function parameters. These include insulin resistance (HOMA-IR), inflammation, oxidative stress, and cardiopulmonary variables (FVC, FEV1, LV-EF, CCA distensibility). MIS-ATP showed significant correlations with HOMA-IR and pulmonary functions, indicating its direct impact of MIS-ATP on metabolic and pulmonary health. MIS-ROS correlated with oxidative stress markers and CCA distensibility, suggesting a role in systemic inflammatory responses. This study highlights the intricate relationships between environmental pollutant mixture and cardiopulmonary health in MetS as indicated by biomarkers of POP exposure in the elderly population, suggesting POP exposure may influence MetS onset and progression through mitochondrial dysfunction.
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Affiliation(s)
- Youngmi Kim Pak
- Department of Physiology, Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Kyung Hee University School of Medicine, Seoul, South Korea
- Department of Neuroscience, Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Kyung Hee University School of Medicine, Seoul, South Korea
| | - Suyeol Im
- Department of Neuroscience, Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Kyung Hee University School of Medicine, Seoul, South Korea
| | - Hoon Sung Choi
- Department of Internal Medicine, Chung Ang University College of Medicine, Seoul, South Korea
| | - Lars Lind
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Monica Lind
- Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden
| | - Hong Kyu Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
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2
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The effects of N-acetylcysteine administration on metabolic status and serum adiponectin levels in patients with metabolic syndrome: A randomized, double-blind, placebo-controlled trial. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.105299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
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3
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Mitsis A, Kadoglou NPE, Lambadiari V, Alexiou S, Theodoropoulos KC, Avraamides P, Kassimis G. Prognostic role of inflammatory cytokines and novel adipokines in acute myocardial infarction: An updated and comprehensive review. Cytokine 2022; 153:155848. [PMID: 35301174 DOI: 10.1016/j.cyto.2022.155848] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/23/2022] [Accepted: 02/28/2022] [Indexed: 12/19/2022]
Abstract
Acute myocardial infarction (AMI) is one of the major causes of morbidity and mortality worldwide. The inflammation response during and after AMI is common and seems to play a key role in the peri-AMI period, related with ischaemia-reperfusion injury, adverse cardiac remodelling, infarct size and poor prognosis. In this article, we provide an updated and comprehensive overview of the most important cytokines and adipokines involved in the complex pathophysiology mechanisms in AMI, summarizing their prognostic role post-AMI. Data so far support that elevated levels of the major proinflammatory cytokines TNFα, IL-6 and IL-1 and the adipokines adiponectin, visfatin and resistin, are linked to high mortality and morbidity. In contrary, there is evidence that anti-inflammatory cytokines and adipokines as IL-10, omentin-1 and ghrelin can suppress the AMI-induced inflammatory response and are correlated with better prognosis. Mixed data make unclear the role of the novel adipokines leptin and apelin. After all, imbalance of pro-inflammatory and anti-inflammatory cytokines may result in worst AMI prognosis. The incorporation of these inflammation biomarkers in established prognostic models could further improve their prognostic power improving overall the management of AMI patients.
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Affiliation(s)
- Andreas Mitsis
- Cardiology Department, Nicosia General Hospital, Cyprus.
| | | | - Vaia Lambadiari
- Second Department of Internal Medicine, Research Institute and Diabetes Centre, Athens University Medical School, Attikon University General Hospital, Athens, Greece
| | - Sophia Alexiou
- Second Cardiology Department, "Hippokration" Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | | | | | - George Kassimis
- Second Cardiology Department, "Hippokration" Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
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4
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Corken A, Thakali KM. Maternal Obesity Programming of Perivascular Adipose Tissue and Associated Immune Cells: An Understudied Area With Few Answers and Many Questions. Front Physiol 2022; 12:798987. [PMID: 35126181 PMCID: PMC8815821 DOI: 10.3389/fphys.2021.798987] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 12/09/2021] [Indexed: 12/11/2022] Open
Abstract
At present, the worldwide prevalence of obesity has become alarmingly high with estimates foreshadowing a continued escalation in the future. Furthermore, there is growing evidence attributing an individual’s predisposition for developing obesity to maternal health during gestation. Currently, 60% of pregnancies in the US are to either overweight or obese mothers which in turn contributes to the persistent rise in obesity rates. While obesity itself is problematic, it conveys an increased risk for several diseases such as diabetes, inflammatory disorders, cancer and cardiovascular disease (CVD). Additionally, as we are learning more about the mechanisms underlying CVD, much attention has been brought to the role of perivascular adipose tissue (PVAT) in maintaining cardiovascular health. PVAT regulates vascular tone and for a significant number of individuals, obesity elicits PVAT disruption and dysregulation of vascular function. Obesity elicits changes in adipocyte and leukocyte populations within PVAT leading to an inflammatory state which promotes vasoconstriction thereby aiding the onset/progression of CVD. Our current understanding of obesity, PVAT and CVD has only been examined at the individual level without consideration for a maternal programming effect. It is unknown if maternal obesity affects the propensity for PVAT remodeling in the offspring, thereby enhancing the obesity/CVD link, and what role PVAT leukocytes play in this process. This perspective will focus on the maternal contribution of the interplay between obesity, PVAT disruption and CVD and will highlight the leukocyte/PVAT interaction as a novel target to stem the tide of the current obesity epidemic and its secondary health consequences.
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Affiliation(s)
- Adam Corken
- Arkansas Children’s Nutrition Center, Little Rock, AR, United States
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Keshari M. Thakali
- Arkansas Children’s Nutrition Center, Little Rock, AR, United States
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, United States
- *Correspondence: Keshari M. Thakali,
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5
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Herpich C, Kochlik B, Haß U, Weber D, Grune T, Norman K. Altered Adiponectin Response in Older Women Following Dextrose and High-Fat Dietary Challenges. Mol Nutr Food Res 2021; 65:e2100487. [PMID: 34288404 DOI: 10.1002/mnfr.202100487] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 07/02/2021] [Indexed: 12/25/2022]
Abstract
SCOPE Despite its beneficial properties, higher adiponectin concentrations are paradoxically associated with mortality in advanced age. Several mechanisms are being discussed. However, little is known about postprandial regulation of adiponectin in older adults. We assessed age-specific differences of the adiponectin response to different test meals considering potential determinants. METHODS AND RESULTS Older (n = 20) and younger (n = 22) women are randomized to a dextrose (DEX) or high-fat (HF) dietary challenge. Postprandial adiponectin and fibroblast growth factor 21 (FGF21) concentrations are measured before and 60, 120, 240 min after ingestion. We assessed postprandial changes and group differences using linear mixed models controlled for possible determinants. In younger women, postprandial adiponectin remains stable after both test meals. In contrast, adiponectin increases following DEX and decreases after HF in older women, irrespective of control variables. Postprandial adiponectin is positively associated with malondialdehyde and inversely associated with interleukin-6 following DEX and also negatively associated with metabolic parameters after both test meals. In older women, elevated postprandial FGF21 concentrations are associated with a higher adiponectin response (β = 30.7, 95% CI 10.6-50.8, p = 0.007). CONCLUSIONS Adiponectin response is associated with type of dietary challenge, age, and FGF21 response. Age-group differences are partly attributable to metabolic parameters and oxidative stress.
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Affiliation(s)
- Catrin Herpich
- Department of Nutrition and Gerontology, German Institute of Human Nutrition, Potsdam - Rehbrücke, Nuthetal, Germany.,University of Potsdam, Institute of Nutritional Science, Nuthetal, Germany
| | - Bastian Kochlik
- Department of Nutrition and Gerontology, German Institute of Human Nutrition, Potsdam - Rehbrücke, Nuthetal, Germany
| | - Ulrike Haß
- Department of Nutrition and Gerontology, German Institute of Human Nutrition, Potsdam - Rehbrücke, Nuthetal, Germany.,University of Potsdam, Institute of Nutritional Science, Nuthetal, Germany
| | - Daniela Weber
- Department of Molecular Toxicology, German Institute of Human Nutrition, Potsdam - Rehbrücke, Nuthetal, Germany
| | - Tilman Grune
- University of Potsdam, Institute of Nutritional Science, Nuthetal, Germany.,Department of Molecular Toxicology, German Institute of Human Nutrition, Potsdam - Rehbrücke, Nuthetal, Germany.,German Center for Diabetes Research (DZD), Muenchen-Neuherberg, Germany.,German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.,Department of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, 1090, Austria
| | - Kristina Norman
- Department of Nutrition and Gerontology, German Institute of Human Nutrition, Potsdam - Rehbrücke, Nuthetal, Germany.,University of Potsdam, Institute of Nutritional Science, Nuthetal, Germany.,German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.,Department of Geriatrics and Medical Gerontology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
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6
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Liu D, Wu L, Gao Q, Long X, Hou X, Qian L, Ni J, Fang Q, Li H, Jia W. FGF21/adiponectin ratio predicts deterioration in glycemia: a 4.6-year prospective study in China. Cardiovasc Diabetol 2021; 20:157. [PMID: 34321008 PMCID: PMC8320224 DOI: 10.1186/s12933-021-01351-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Accepted: 07/21/2021] [Indexed: 12/29/2022] Open
Abstract
Background The fibroblast growth factor (FGF) 21-adiponectin pathway is involved in the regulation of insulin resistance. However, the relationship between the FGF21-adiponectin pathway and type 2 diabetes in humans is unclear. Here, we investigated the association of FGF21/adiponectin ratio with deterioration in glycemia in a prospective cohort study. Methods We studied 6361 subjects recruited from the prospective Shanghai Nicheng Cohort Study in China. The association between baseline FGF21/adiponectin ratio and new-onset diabetes and incident prediabetes was evaluated using multiple logistic regression analysis. Results At baseline, FGF21/adiponectin ratio levels increased progressively with the deterioration in glycemic control from normal glucose tolerance to prediabetes and diabetes (p for trend < 0.001). Over a median follow-up of 4.6 years, 195 subjects developed new-onset diabetes and 351 subjects developed incident prediabetes. Elevated baseline FGF21/adiponectin ratio was a significant predictor of new-onset diabetes independent of traditional risk factors, especially in subjects with prediabetes (odds ratio, 1.367; p = 0.001). Moreover, FGF21/adiponectin ratio predicted incident prediabetes (odds ratio, 1.185; p = 0.021) while neither FGF21 nor adiponectin were independent predictors of incident prediabetes (both p > 0.05). Furthermore, net reclassification improvement and integrated discrimination improvement analyses showed that FGF21/adiponectin ratio provided a better performance in diabetes risk prediction than the use of FGF21 or adiponectin alone. Conclusions FGF21/adiponectin ratio independently predicted the onset of prediabetes and diabetes, with the potential to be a useful biomarker of deterioration in glycemia. Supplementary Information The online version contains supplementary material available at 10.1186/s12933-021-01351-1.
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Affiliation(s)
- Dan Liu
- Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.,Department of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Liang Wu
- Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Qiongmei Gao
- Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Xiaoxue Long
- Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.,Department of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xuhong Hou
- Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Lingling Qian
- Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Jiacheng Ni
- Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Qichen Fang
- Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Huating Li
- Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
| | - Weiping Jia
- Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
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7
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García-Marín LM, Campos AI, Kho PF, Martin NG, Cuéllar-Partida G, Rentería ME. Phenome-wide screening of GWAS data reveals the complex causal architecture of obesity. Hum Genet 2021; 140:1253-1265. [PMID: 34057592 DOI: 10.1007/s00439-021-02298-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 05/26/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVE In the present study, we sought to identify causal relationships between obesity and other complex traits and conditions using a data-driven hypothesis-free approach that uses genetic data to infer causal associations. METHODS We leveraged available summary-based genetic data from genome-wide association studies on 1498 phenotypes and applied the latent causal variable method (LCV) between obesity and all traits. RESULTS We identified 110 traits causally associated with obesity. Of those, 109 were causal outcomes of obesity, while only leg pain in calves was a causal determinant of obesity. Causal outcomes of obesity included 26 phenotypes associated with cardiovascular diseases, 22 anthropometric measurements, nine with the musculoskeletal system, nine with behavioural or lifestyle factors including loneliness or isolation, six with respiratory diseases, five with body bioelectric impedances, four with psychiatric phenotypes, four related to the nervous system, four with disabilities or long-standing illness, three with the gastrointestinal system, three with use of analgesics, two with metabolic diseases, one with inflammatory response and one with the neurodevelopmental disorder ADHD, among others. In particular, some causal outcomes of obesity included hypertension, stroke, ever having a period of extreme irritability, low forced vital capacity and forced expiratory volume, diseases of the musculoskeletal system, diabetes, carpal tunnel syndrome, loneliness or isolation, high leukocyte count, and ADHD. CONCLUSIONS Our results indicate that obesity causally affects a wide range of traits and comorbid diseases, thus providing an overview of the metabolic, physiological, and neuropsychiatric impact of obesity on human health.
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Affiliation(s)
- Luis M García-Marín
- Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
- School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Adrián I Campos
- Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
- School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Pik-Fang Kho
- Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
- School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia
| | - Nicholas G Martin
- Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - Gabriel Cuéllar-Partida
- University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD, Australia.
- 23andMe, Inc, Sunnyvale, CA, USA.
| | - Miguel E Rentería
- Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
- School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
- School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.
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8
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Alkazemi D, Rahman A, Habra B. Alterations in glutathione redox homeostasis among adolescents with obesity and anemia. Sci Rep 2021; 11:3034. [PMID: 33542364 PMCID: PMC7862436 DOI: 10.1038/s41598-021-82579-5] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 12/29/2020] [Indexed: 12/20/2022] Open
Abstract
The reduced (GSH)-to-oxidized (GSSG) glutathione ratio represents a dynamic balance between oxidants and antioxidants. However, redox status in adolescents with obesity and anemia has not been investigated. This study investigated the association of erythrocyte GSH redox status (GSH, GSH:GSSG ratio, and glutathione peroxidase [GPx] activity) with anemia and adiposity in adolescents. This case–control study nested in a cross-sectional study enrolled 524 adolescents (268 boys; 256 girls). The prevalence of anemia in overweight and obesity (OWOB) was 5.2% in boys and 11.7% in girls. The GSH:GSSG ratio and GPx activity were significantly higher in girls than in boys (p < 0.001), in anemic than in non-anemic subjects (p < 0.001), and in OWOB than in normal-weight subjects (p < 0.001). Similarly, significantly higher GSH: GSSG level (p < 0.001) and GPx activity (p < 0.001) were found in subjects with 90th percentile waist circumference than in those with < 90th percentile. GPx and GSH:GSSG were positively associated with anemia after adjusting for age, sex, and body mass index (adjusted odds ratio, adjOR [95% confidence interval, CI] 2.18 [1.44–3.29]) or tertiles (adjOR [95% CI], T3 = 2.49 [1.03–6.01]). A similar association was noted for GSH and GPx. A compensatory increased redox defense mechanism exists in anemia and obesity among adolescents without metabolic disturbances.
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Affiliation(s)
- Dalal Alkazemi
- Department of Food Science and Nutrition, College of Life Sciences, Kuwait University, AlShadadiyah, Kuwait.
| | - Abdur Rahman
- Department of Food Science and Nutrition, College of Life Sciences, Kuwait University, AlShadadiyah, Kuwait
| | - Banan Habra
- Department of Food Science and Nutrition, College of Life Sciences, Kuwait University, AlShadadiyah, Kuwait
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9
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Flavonoids in adipose tissue inflammation and atherosclerosis: one arrow, two targets. Clin Sci (Lond) 2020; 134:1403-1432. [PMID: 32556180 DOI: 10.1042/cs20200356] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 06/09/2020] [Accepted: 06/10/2020] [Indexed: 02/07/2023]
Abstract
Flavonoids are polyphenolic compounds naturally occurring in fruits and vegetables, in addition to beverages such as tea and coffee. Flavonoids are emerging as potent therapeutic agents for cardiovascular as well as metabolic diseases. Several studies corroborated an inverse relationship between flavonoid consumption and cardiovascular disease (CVD) or adipose tissue inflammation (ATI). Flavonoids exert their anti-atherogenic effects by increasing nitric oxide (NO), reducing reactive oxygen species (ROS), and decreasing pro-inflammatory cytokines. In addition, flavonoids alleviate ATI by decreasing triglyceride and cholesterol levels, as well as by attenuating inflammatory mediators. Furthermore, flavonoids inhibit synthesis of fatty acids and promote their oxidation. In this review, we discuss the effect of the main classes of flavonoids, namely flavones, flavonols, flavanols, flavanones, anthocyanins, and isoflavones, on atherosclerosis and ATI. In addition, we dissect the underlying molecular and cellular mechanisms of action for these flavonoids. We conclude by supporting the potential benefit for flavonoids in the management or treatment of CVD; yet, we call for more robust clinical studies for safety and pharmacokinetic values.
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10
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Ibrahim Fouad G. Synergistic anti-atherosclerotic role of combined treatment of omega-3 and co-enzyme Q10 in hypercholesterolemia-induced obese rats. Heliyon 2020; 6:e03659. [PMID: 32258512 PMCID: PMC7118318 DOI: 10.1016/j.heliyon.2020.e03659] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 12/16/2019] [Accepted: 03/20/2020] [Indexed: 01/13/2023] Open
Abstract
Hypercholesterolemia is a metabolic disorder associated with atherosclerosis. This study aimed to investigate the effects of omega-3 and/or coenzyme Q10 (CoQ10) on hypercholesterolemia-induced atherosclerosis. Rats were divided into five groups; (1): served as the negative control, (2): served as hypercholesterolemic (HC) control, (3): HC-rats administrated omega-3 orally, (4): HC-rats administrated CoQ10 orally, and (5): HC-rats administered the combination treatment of both omega-3 and CoQ10. Lipid profile was assayed and cardiovascular risk indices were calculated. Serum levels of Adiponectin (APN) and creatine kinase (CK-MB) were determined using ELISA. Besides, oxidative stress markers, malondialdehyde (MDA), nitric oxide (NO) and glutathione (GSH) were assayed in the heart homogenate. Histopathological investigation of the aortae and heart tissues were investigated. The results revealed that atherogenic HC-rats demonstrated a significant elevation in lipid profiles, except for HDL-C, along with decreased levels of APN, but increased CK-MB activities. Hypercholesterolemia increased lipid peroxidation, reduced NO production, and decreased GSH content in the cardiac tissue. Treatment of atherogenic HC-rats with omega-3 and/or CoQ10 improved dyslipidemia and ameliorated most of the HC-induced biochemical and histopathological changes. The histological observations of aortae and cardiac tissues validated our biochemical results. We concluded that the combined treatment of nutraceuticals such as omega-3 and CoQ10 demonstrated the best outcome, demonstrating their anti-hyperlipidemic, cardioprotective, and atheroprotective potentials. Together, this study supports a beneficial role of dietary co-administration of omega-3 and CoQ10 in obese patients who are prone to develop cardiovascular disorders.
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Affiliation(s)
- Ghadha Ibrahim Fouad
- Department of Therapeutic Chemistry, National Research Centre, 33 El-Bohouth Street, Dokki, Cairo, 12622, Egypt
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11
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Kaur Y, Wang DX, Liu HY, Meyre D. Comprehensive identification of pleiotropic loci for body fat distribution using the NHGRI-EBI Catalog of published genome-wide association studies. Obes Rev 2019; 20:385-406. [PMID: 30565845 DOI: 10.1111/obr.12806] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 10/05/2018] [Accepted: 10/15/2018] [Indexed: 12/22/2022]
Abstract
We conducted a hypothesis-free cross-trait analysis for waist-to-hip ratio adjusted for body mass index (WHRadjBMI ) loci derived through genome-wide association studies (GWAS). Summary statistics from published GWAS were used to capture all WHRadjBMI single-nucleotide polymorphisms (SNPs), and their proxy SNPs were identified. These SNPs were used to extract cross-trait associations between WHRadjBMI SNPs and other traits through the NHGRI-EBI GWAS Catalog. Pathway analysis was conducted for pleiotropic WHRadjBMI SNPs. We found 160 WHRadjBMI SNPs and 3675 proxy SNPs. Cross-trait analysis identified 239 associations, of which 100 were for obesity traits. The remaining 139 associations were filtered down to 101 unique linkage disequilibrium block associations, which were grouped into 13 categories: lipids, red blood cell traits, white blood cell counts, inflammatory markers and autoimmune diseases, type 2 diabetes-related traits, adiponectin, cancers, blood pressure, height, neuropsychiatric disorders, electrocardiography changes, urea measurement, and others. The highest number of cross-trait associations were found for triglycerides (n = 10), high-density lipoprotein cholesterol (n = 9), and reticulocyte counts (n = 8). Pathway analysis for WHRadjBMI pleiotropic SNPs found immune function pathways as the top canonical pathways. Results from our original methodology indicate a novel genetic association between WHRadjBMI and reticulocyte counts and highlight the pleiotropy between abdominal obesity, immune pathways, and other traits.
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Affiliation(s)
- Yuvreet Kaur
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.,Faculty of Medicine, University of Toronto, Toronto, Canada
| | - Dominic X Wang
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.,Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
| | - Hsin-Yen Liu
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.,Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
| | - David Meyre
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.,Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada
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12
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Qi XY, Qu SL, Xiong WH, Rom O, Chang L, Jiang ZS. Perivascular adipose tissue (PVAT) in atherosclerosis: a double-edged sword. Cardiovasc Diabetol 2018; 17:134. [PMID: 30305178 PMCID: PMC6180425 DOI: 10.1186/s12933-018-0777-x] [Citation(s) in RCA: 140] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Accepted: 10/06/2018] [Indexed: 02/06/2023] Open
Abstract
Perivascular adipose tissue (PVAT), the adipose tissue that surrounds most of the vasculature, has emerged as an active component of the blood vessel wall regulating vascular homeostasis and affecting the pathogenesis of atherosclerosis. Although PVAT characteristics resemble both brown and white adipose tissues, recent evidence suggests that PVAT develops from its own distinct precursors implying a closer link between PVAT and vascular system. Under physiological conditions, PVAT has potent anti-atherogenic properties mediated by its ability to secrete various biologically active factors that induce non-shivering thermogenesis and metabolize fatty acids. In contrast, under pathological conditions (mainly obesity), PVAT becomes dysfunctional, loses its thermogenic capacity and secretes pro-inflammatory adipokines that induce endothelial dysfunction and infiltration of inflammatory cells, promoting atherosclerosis development. Since PVAT plays crucial roles in regulating key steps of atherosclerosis development, it may constitute a novel therapeutic target for the prevention and treatment of atherosclerosis. Here, we review the current literature regarding the roles of PVAT in the pathogenesis of atherosclerosis.
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Affiliation(s)
- Xiao-Yan Qi
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, University of South China, Hengyang, 421001 China
| | - Shun-Lin Qu
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, University of South China, Hengyang, 421001 China
| | - Wen-Hao Xiong
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, University of South China, Hengyang, 421001 China
| | - Oren Rom
- Cardiovascular Research Center, University of Michigan, Ann Arbor, MI USA
| | - Lin Chang
- Cardiovascular Research Center, University of Michigan, Ann Arbor, MI USA
| | - Zhi-Sheng Jiang
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, University of South China, Hengyang, 421001 China
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Tomeleri CM, Cavaglieri CR, de Souza MF, Cavalcante EF, Antunes M, Nabbuco HCG, Venturini D, Barbosa DS, Silva AM, Cyrino ES. Phase angle is related with inflammatory and oxidative stress biomarkers in older women. Exp Gerontol 2018; 102:12-18. [PMID: 29197561 DOI: 10.1016/j.exger.2017.11.019] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Revised: 11/22/2017] [Accepted: 11/27/2017] [Indexed: 01/10/2023]
Abstract
BACKGROUND The aim of this study was to examine the relation between phase angle (PhA) and inflammatory and oxidative stress biomarkers in older women. METHODS One hundred and fifty-five physically independent older women participated in this study (67.7±5.7years, 27.0±4.4kg/m2). Inflammatory markers included interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and acute phase reactive protein (CRP). Oxidative stress biomarkers comprised superoxide dismutase (SOD), catalase (CAT), advanced oxidation protein products (AOPP), and total radical-trapping antioxidant potential (TRAP). A spectral bioelectrical impedance device was used to estimate resistance (R) and reactance (Xc) at frequency 50kHz, and subsequently PhA was calculated as arc-tangent (Xc/R)×180°/π. The covariates appendicular lean soft-tissue (ALST), trunk fat mass, and total body fat were determined by whole-body dual-energy X-ray absorptiometry. Linear regression analysis was conducted to further test if PhA is related with the dependent variables, after adjusting for potential covariates. RESULTS After controlling for the potential covariates (age, trunk fat mass, ALST, and number of diseases) PhA exhibited a significant inverse relation with IL-6 (β=-0.97; P<0.01), TNF-α (β=-0.84; P<0.01), and CRP (β=-0.58; P<0.01). Conversely, PhA was significantly related to CAT (β=7.27; P<0.01), SOD (β=10.55; P<0.01) and TRAP (β=73.08; P<0.01). The AOPP did not demonstrate a significant correlation with PhA (P>0.05). CONCLUSION Our findings show that PhA is a simple and relevant explanatory variable which is related inflammatory and stress oxidative markers in physically independent older women, regardless of age, number of diseases, and body composition.
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Affiliation(s)
- Crisieli Maria Tomeleri
- Metabolism, Nutrition, and Exercise Laboratory, Londrina State University, Londrina, Brazil; Exercise Physiology Laboratory, Faculty of Physical Education, University of Campinas - Unicamp, Brazil.
| | - Cláudia Regina Cavaglieri
- Exercise Physiology Laboratory, Faculty of Physical Education, University of Campinas - Unicamp, Brazil
| | - Mariana Ferreira de Souza
- Metabolism, Nutrition, and Exercise Laboratory, Londrina State University, Londrina, Brazil; Department of Physical Education, Federal University of Vale do São Francisco, Petrolina, Brazil
| | | | - Melissa Antunes
- Metabolism, Nutrition, and Exercise Laboratory, Londrina State University, Londrina, Brazil
| | | | - Danielle Venturini
- Metabolism, Nutrition, and Exercise Laboratory, Londrina State University, Londrina, Brazil; Clinical Analyses Laboratory, Londrina State University, Londrina, Brazil
| | - Decio Sabbatini Barbosa
- Metabolism, Nutrition, and Exercise Laboratory, Londrina State University, Londrina, Brazil; Clinical Analyses Laboratory, Londrina State University, Londrina, Brazil
| | - Analiza Mônica Silva
- Exercise and Health Laboratory, CIPER, Faculdade de Motricidade Humana, Universidade de Lisboa, Cruz-Quebrada, Portugal
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Gradinaru D, Margina D, Borsa C, Ionescu C, Ilie M, Costache M, Dinischiotu A, Prada GI. Adiponectin: possible link between metabolic stress and oxidative stress in the elderly. Aging Clin Exp Res 2017; 29:621-629. [PMID: 27688246 DOI: 10.1007/s40520-016-0629-z] [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: 03/13/2016] [Accepted: 09/15/2016] [Indexed: 12/21/2022]
Abstract
OBJECTIVE The aim of this study was to evaluate the relationships between the serum levels of adiponectin and systemic oxidative stress exerted on lipids, proteins, as well as endothelial function and cardiovascular diseases (CVD) risk markers, in elderly subjects with metabolic syndrome (MS). METHODS The serum advanced glycation and oxidation protein products, low-density lipoprotein susceptibility to oxidation (oxLDL), nitric oxide metabolic pathway products (NOx), serum lipid peroxidation, as well as total antioxidant/oxidative capacity (TAC/TOC), were analyzed in elderly subjects with MS (n = 44), compared to aged-matched control (n = 39). RESULTS We pointed out significantly lower levels of adiponectin in elderly MS subjects concomitantly with significantly higher levels of oxidative stress and CVD risk markers. Significant positive correlations were found between serum adiponectin levels and HDL-cholesterol (p < 0.05) and the total cholesterol/LDL-cholesterol ratio (p < 0.01). Additionally, adiponectin levels were significantly inversely associated with insulin resistance index (HOMA-IR, r = -0.348; p < 0.05) and serum lipid peroxidation (r = -0.337; p < 0.05), and significantly positively with the antioxidant capacity (TAC, r = 0.339; p < 0.05). Conversely, adiponectin levels were significantly negatively (r = -0.310; p < 0.05) associated with serum uric acid concentration. CONCLUSIONS The major protective role of adiponectin versus stress related to an impaired glucose and lipid metabolism suggests that adiponectin plays a critical role in adiposity-related metabolic stress and redox homeostasis.
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Affiliation(s)
- Daniela Gradinaru
- Department of Biochemistry, Faculty of Pharmacy, Carol Davila - University of Medicine and Pharmacy, 6 Taian Vuia street, sector 2, 020956, Bucharest, Romania.
| | - Denisa Margina
- Department of Biochemistry, Faculty of Pharmacy, Carol Davila - University of Medicine and Pharmacy, 6 Taian Vuia street, sector 2, 020956, Bucharest, Romania
| | - Claudia Borsa
- Ana Aslan - National Institute of Gerontology and Geriatrics, 9 Caldarusani street, sector 1, PO Box 2-4, 011241, Bucharest, Romania
| | - Cristina Ionescu
- Ana Aslan - National Institute of Gerontology and Geriatrics, 9 Caldarusani street, sector 1, PO Box 2-4, 011241, Bucharest, Romania
| | - Mihaela Ilie
- Department of Biochemistry, Faculty of Pharmacy, Carol Davila - University of Medicine and Pharmacy, 6 Taian Vuia street, sector 2, 020956, Bucharest, Romania
| | - Marieta Costache
- Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, sector 5, 050107, Bucharest, Romania
| | - Anca Dinischiotu
- Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, sector 5, 050107, Bucharest, Romania
| | - Gabriel-Ioan Prada
- Ana Aslan - National Institute of Gerontology and Geriatrics, 9 Caldarusani street, sector 1, PO Box 2-4, 011241, Bucharest, Romania
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Liberale L, Bonaventura A, Vecchiè A, Casula M, Dallegri F, Montecucco F, Carbone F. The Role of Adipocytokines in Coronary Atherosclerosis. Curr Atheroscler Rep 2017; 19:10. [PMID: 28185154 DOI: 10.1007/s11883-017-0644-3] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
PURPOSE OF REVIEW The aim of this review is to overview the pathophysiological role of adipocytokines in atherogenesis, focusing on their potential role as biomarkers of coronary disease. RECENT FINDINGS Several lines of evidence indicated adipose tissue not only as depot but rather as an endocrine organ. In this context, the balance between pro- and anti-inflammatory adipocytokines has been shown to critically regulate vascular homeostasis in both physiological and pathophysiological conditions. Overweight and obesity are characterized by dysfunctional adipose tissue and then the prevalence of pro-inflammatory mediators, with a detrimental effect on vascular health. As opposite to adiponectin, pro-inflammatory adipocytokines, such as leptin and resistin, promote endothelial dysfunction and inflammatory processes involved in atherosclerotic plaque progression and vulnerability. Therefore, many adipocytokines have been investigated as potential biomarkers of cardiovascular (CV) risk, but their role has not yet been clearly established. Furthermore, the perivascular adipose tissue recently emerged as a critical modulator of atherosclerotic processes, due to the close interaction with the underlying vascular tissue. The ongoing discovery of new adipocytokines and the complex pathophysiological role of the different adipose tissue depots strongly contribute to define the complexity of adipocytokines network. Understanding those complex interactions may allow determining new potential biomarkers of CV risk and potential therapeutic targets.
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Affiliation(s)
- Luca Liberale
- Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132, Genoa, Italy
| | - Aldo Bonaventura
- Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132, Genoa, Italy
| | - Alessandra Vecchiè
- Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132, Genoa, Italy
| | - Matteo Casula
- Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132, Genoa, Italy
| | - Franco Dallegri
- Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132, Genoa, Italy
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa and IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, 10 Largo Benzi, 16132, Genoa, Italy
| | - Fabrizio Montecucco
- Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132, Genoa, Italy
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa and IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, 10 Largo Benzi, 16132, Genoa, Italy
- Centre of Excellence for Biomedical Research (CEBR), University of Genoa, 9 Viale Benedetto XV, 16132, Genoa, Italy
| | - Federico Carbone
- Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132, Genoa, Italy.
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Ding Y, Zhang D, Wang B, Zhang Y, Wang L, Chen X, Li M, Tang Z, Wang C. APPL1-mediated activation of STAT3 contributes to inhibitory effect of adiponectin on hepatic gluconeogenesis. Mol Cell Endocrinol 2016; 433:12-9. [PMID: 27246173 DOI: 10.1016/j.mce.2016.05.021] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Revised: 05/26/2016] [Accepted: 05/27/2016] [Indexed: 12/19/2022]
Abstract
Adiponectin has been shown to suppress hepatic gluconeogenesis. However, the signaling pathways underlying its action remain ill-defined. The purpose of this study was to examine the potential role of APPL1 in mediating anti-gluconeogenic ability of adiponectin. Primary hepatocytes were isolated from male C57BL/6 mice. Western blot and RT-PCR were performed to detect protein expression and mRNA level, respectively. The protein-protein association was determined by immunoprecipitation and GST pull-down assay. We found that APPL1 protein levels were negatively associated with expressions of proteins and mRNAs of gluconeogenesis enzymes under stimulation with adiponectin. In addition, adiponectin-stimulated STAT3 phosphorylation and acetylation were positively regulated by APPL1 and negative regulated by SirT1. Pharmacological and genetic inhibition of STAT3 mitigated impact of adiponectin on hepatic gluconeogenesis. Furthermore, adiponectin administration facilitated the binding of APPL1 to SirT1 and suppressed the association of SirT1 with STAT3. Taken together, our study showed that APPL1-SirT1-STAT3 pathway mediated adiponectin signaling in primary hepatocytes. This new finding provides a novel mechanism by which adiponectin suppresses hepatic gluconeogenesis.
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Affiliation(s)
- Youming Ding
- Department of Hepatobiliary & Laparoscopic Surgery, Wuhan University Renmin Hospital, Wuhan 430060, China
| | - Deling Zhang
- Department of Pathology & Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China
| | - Bin Wang
- Department of Hepatobiliary & Laparoscopic Surgery, Wuhan University Renmin Hospital, Wuhan 430060, China
| | - Yemin Zhang
- Department of Pathology & Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China
| | - Lei Wang
- Department of Hepatobiliary & Laparoscopic Surgery, Wuhan University Renmin Hospital, Wuhan 430060, China
| | - Xiaoyan Chen
- Department of Hepatobiliary & Laparoscopic Surgery, Wuhan University Renmin Hospital, Wuhan 430060, China
| | - Mingxin Li
- Department of Pathology & Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China
| | - Zhao Tang
- Department of Pathology & Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China
| | - Changhua Wang
- Department of Pathology & Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
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Cord Blood Adiponectin and Visfatin Concentrations in relation to Oxidative Stress Markers in Neonates Exposed and Nonexposed In Utero to Tobacco Smoke. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:4569108. [PMID: 27525051 PMCID: PMC4971318 DOI: 10.1155/2016/4569108] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 06/06/2016] [Accepted: 06/16/2016] [Indexed: 12/17/2022]
Abstract
Aims. Maternal smoking is considered as a source of oxidative stress, which has been implicated to disrupted adipokines expression in adipose tissue. We examined the relationship between selected adipokines and markers of oxidative stress/antioxidant defence in the umbilical cord of neonates exposed and nonexposed in utero to tobacco smoke. Methods. Subjects including 85 healthy neonates (born to 41 smokers and 44 nonsmokers) were tested for adiponectin, visfatin, oxidized low density lipoprotein (ox-LDL), total oxidant capacity (TOC), and total antioxidant capacity (TAC). Results. Cord serum visfatin, ox-LDL, and TOC were significantly higher (p < 0.001) but adiponectin and TAC were lower (p < 0.001 and p < 0.05, resp.) in smoking group than in tobacco abstinents. In whole group of children (adjusted for smoking status, gender, and birth weight) adiponectin showed negative and visfatin positive correlations with ox-LDL. In the model estimated separately for smokers ox-LDL explained 36% of adiponectin and 35.5% of visfatin variance, while in the model of nonsmokers it explained 36.8% and 69.4%, respectively. Conclusion. Maternal smoking enhances oxidative status and depletes antioxidant potential in newborns. Lower level of adiponectin and higher visfatin concentration seem to be related with a less beneficial oxidative stress profile and higher level of lipid peroxidation in neonates exposed and nonexposed in utero to tobacco smoke.
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Di Rosa M, Malaguarnera L. Chitinase 3 Like-1: An Emerging Molecule Involved in Diabetes and Diabetic Complications. Pathobiology 2016; 83:228-242. [PMID: 27189062 DOI: 10.1159/000444855] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Accepted: 02/18/2016] [Indexed: 01/05/2025] Open
Abstract
Chitinase 3 like-1 (CHI3L1) is a chitinase-like protein member of family 18 chitinases, expressed in innate immune cells and involved in endothelial dysfunction and tissue remodelling. Since CHI3L1 is highly expressed in a variety of inflammatory diseases of infectious and non-infectious aetiology, it is recognised as a non-invasive prognostic biomarker for inflammation. A variety of studies revealing the increase in CHI3L1 levels in obesity, insulin resistance and in pathological conditions, such as atherosclerosis, coronary artery disease, acute ischaemic stroke, nephropathy, diabetic retinopathy and osteolytic processes, have suggested that CHI3L1 may also play a critical role in the evolution and complication of diabetes mellitus (DM). In this review we highlight the impact of CHI3L1 expression in DM and its contribution to the complication of this disease.
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Affiliation(s)
- Michelino Di Rosa
- Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy
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19
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Rebelo F, Farias DR, Struchiner CJ, Kac G. Plasma adiponectin and depressive symptoms during pregnancy and the postpartum period: A prospective cohort study. J Affect Disord 2016; 194:171-9. [PMID: 26826867 DOI: 10.1016/j.jad.2016.01.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Revised: 12/28/2015] [Accepted: 01/08/2016] [Indexed: 12/26/2022]
Abstract
BACKGROUND Some authors have described an inverse association between adiponectin and depression, but this association has not yet been investigated during the perinatal period. OBJECTIVE To evaluate the association between the plasma adiponectin levels and symptoms of depression in women from early pregnancy to 30-45 days postpartum. METHODS A prospective cohort of 235 women was analyzed, with four waves of follow-up: 5-13th, 22-26th, and 30-36th gestational weeks and 30-45 days postpartum. Depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS; cutoff ≥ 11). The plasma adiponectin concentrations were measured using an enzyme-linked immunosorbent assay. The statistical analyses included linear mixed effects regressions to model the association between these time-dependent variables. RESULTS The prevalence of depressive symptoms was 35.5%, 22.8%, 21.8%, and 16.9% and the median (µg/mL) adiponectin levels were 4.8, 4.7, 4.4, and 7.5 in the 1st, 2nd, and 3rd trimesters and the postpartum period, respectively. Women who remained non-depressed throughout the study tended to have higher values of adiponectin throughout pregnancy and the postpartum period compared to those who had depressive symptoms at least once, but this difference was not statistically significant (β=-0.14; p=0.071). There was no statistically significant association between the plasma adiponectin levels and the EPDS scores in the multiple model (β=-0.07; p=0.320). LIMITATIONS Losses to follow-up, different procedures for the blood draws at the prenatal and postpartum visits, and the presence of a nested clinical trial with omega-3 supplementation. CONCLUSION The plasma adiponectin levels were not associated with depressive symptoms during the perinatal period.
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Affiliation(s)
- Fernanda Rebelo
- National School of Public Health, Oswaldo Cruz Foundation, Rua Leopoldo Bulhões, 1480 Manguinhos, Rio de Janeiro, RJ, Brazil; Nutritional Epidemiology Observatory, Department of Social and Applied Nutrition, Institute of Nutrition Josué de Castro. Rio de Janeiro Federal University, Avenida Carlos Chagas Filho, 367/CCS, Bloco J2, sala 29, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ, Brazil
| | - Dayana R Farias
- Nutritional Epidemiology Observatory, Department of Social and Applied Nutrition, Institute of Nutrition Josué de Castro. Rio de Janeiro Federal University, Avenida Carlos Chagas Filho, 367/CCS, Bloco J2, sala 29, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ, Brazil
| | - Claudio J Struchiner
- National School of Public Health, Oswaldo Cruz Foundation, Rua Leopoldo Bulhões, 1480 Manguinhos, Rio de Janeiro, RJ, Brazil
| | - Gilberto Kac
- Nutritional Epidemiology Observatory, Department of Social and Applied Nutrition, Institute of Nutrition Josué de Castro. Rio de Janeiro Federal University, Avenida Carlos Chagas Filho, 367/CCS, Bloco J2, sala 29, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ, Brazil.
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Saad MI, Abdelkhalek TM, Saleh MM, Kamel MA, Youssef M, Tawfik SH, Dominguez H. Insights into the molecular mechanisms of diabetes-induced endothelial dysfunction: focus on oxidative stress and endothelial progenitor cells. Endocrine 2015; 50:537-67. [PMID: 26271514 DOI: 10.1007/s12020-015-0709-4] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Accepted: 07/25/2015] [Indexed: 12/13/2022]
Abstract
Diabetes mellitus is a heterogeneous, multifactorial, chronic disease characterized by hyperglycemia owing to insulin insufficiency and insulin resistance (IR). Recent epidemiological studies showed that the diabetes epidemic affects 382 million people worldwide in 2013, and this figure is expected to be 600 million people by 2035. Diabetes is associated with microvascular and macrovascular complications resulting in accelerated endothelial dysfunction (ED), atherosclerosis, and cardiovascular disease (CVD). Unfortunately, the complex pathophysiology of diabetic cardiovascular damage is not fully understood. Therefore, there is a clear need to better understand the molecular pathophysiology of ED in diabetes, and consequently, better treatment options and novel efficacious therapies could be identified. In the light of recent extensive research, we re-investigate the association between diabetes-associated metabolic disturbances (IR, subclinical inflammation, dyslipidemia, hyperglycemia, dysregulated production of adipokines, defective incretin and gut hormones production/action, and oxidative stress) and ED, focusing on oxidative stress and endothelial progenitor cells (EPCs). In addition, we re-emphasize that oxidative stress is the final common pathway that transduces signals from other conditions-either directly or indirectly-leading to ED and CVD.
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Affiliation(s)
- Mohamed I Saad
- Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt.
- Hudson Institute of Medical Research, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia.
| | - Taha M Abdelkhalek
- Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Moustafa M Saleh
- Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Maher A Kamel
- Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Mina Youssef
- Department of Human Genetics, McGill University, Montreal, QC, Canada
| | - Shady H Tawfik
- Department of Molecular Medicine, University of Padova, Padua, Italy
| | - Helena Dominguez
- Department of Biomedical Sciences, Copenhagen University, Copenhagen, Denmark
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Husain K, Hernandez W, Ansari RA, Ferder L. Inflammation, oxidative stress and renin angiotensin system in atherosclerosis. World J Biol Chem 2015; 6:209-217. [PMID: 26322175 PMCID: PMC4549761 DOI: 10.4331/wjbc.v6.i3.209] [Citation(s) in RCA: 231] [Impact Index Per Article: 23.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 05/15/2015] [Accepted: 06/19/2015] [Indexed: 02/05/2023] Open
Abstract
Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin II (Ang II) and a decrease in nitric oxide. The renin-angiotensin system (RAS), and its primary mediator Ang II, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors (angiotensin-converting enzyme inhibitors)], Ang II receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in ApoE-deficient atherosclerotic mice.
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Husain K, Suarez E, Isidro A, Hernandez W, Ferder L. Effect of paricalcitol and enalapril on renal inflammation/oxidative stress in atherosclerosis. World J Biol Chem 2015; 6:240-248. [PMID: 26322179 PMCID: PMC4549765 DOI: 10.4331/wjbc.v6.i3.240] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2015] [Revised: 03/25/2015] [Accepted: 06/11/2015] [Indexed: 02/05/2023] Open
Abstract
AIM: To investigate the protective effect of paricalcitol and enalapril on renal inflammation and oxidative stress in ApoE-knock out mice.
METHODS: Animals treated for 4 mo as group (1) ApoE-knock out plus vehicle, group (2) ApoE-knock out plus paricalcitol (200 ng thrice a week), (3) ApoE-knock out plus enalapril (30 mg/L), (4) ApoE-knock out plus paricalcitol plus enalapril and (5) normal. Blood pressure (BP) was recorded using tail cuff method. The kidneys were isolated for biochemical assays using spectrophotometer and Western blot analyses.
RESULTS: ApoE-deficient mice developed high BP (127 ± 3 mmHg) and it was ameliorated by enalapril and enalapril plus paricalcitol treatments but not with paricalcitol alone. Renal malondialdehyde concentrations, p22phox, manganese-superoxide dismutase, inducible nitric oxide synthase (NOS), monocyte chemoattractant protein-1, tumor necrosis factor-alpha and transforming growth factor-β1 levels significantly elevated but reduced glutathione, CuZn-SOD and eNOS levels significantly depleted in ApoE-knock out animals compared to normal. Administration of paricalcitol, enalapril and combined together ameliorated the renal inflammation and oxidative stress in ApoE-knock out animals.
CONCLUSION: Paricalcitol and enalapril combo treatment ameliorates renal inflammation as well as oxidative stress in atherosclerotic animals.
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Zhang X, Lerman LO. Obesity and renovascular disease. Am J Physiol Renal Physiol 2015; 309:F273-9. [PMID: 26041447 DOI: 10.1152/ajprenal.00547.2014] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2014] [Accepted: 06/02/2015] [Indexed: 12/19/2022] Open
Abstract
Obesity remains a prominent public health concern. Obesity not only contributes greatly to cardiovascular events but has also been identified to initiate and affect the progression of preexisting chronic kidney disease. The prevalence of renal artery stenosis is growing world-wide, especially in the elderly population and in individuals with atherosclerotic risk factors such as obesity. Prolonged renovascular disease causes inflammation and microvascular remodeling within the post-stenotic kidney, which promote tissue scarring and may account for irreversible renal damage. Obesity has been shown to aggravate kidney damage via several pathways, including exacerbation of microvascular regression and renal cell injury mediated by adipocytes and insulin resistance, thereby worsening the structural and functional outcomes of the kidney in renovascular disease. Dietary modification and inhibition of the renin-angiotensin-aldosterone system have been shown to alleviate obesity-induced tissue injury and remodeling. Possibly, angiogenic factors may boost microvascular repair in the ischemic kidney in the obesity milieu. Novel therapeutic interventions targeting deleterious pathways that are activated by obesity and responsible for kidney damage need to be explored in future studies.
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Affiliation(s)
- Xin Zhang
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota; and
| | - Lilach O Lerman
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota; and Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
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Omodei D, Pucino V, Labruna G, Procaccini C, Galgani M, Perna F, Pirozzi D, De Caprio C, Marone G, Fontana L, Contaldo F, Pasanisi F, Matarese G, Sacchetti L. Immune-metabolic profiling of anorexic patients reveals an anti-oxidant and anti-inflammatory phenotype. Metabolism 2015; 64:396-405. [PMID: 25500208 DOI: 10.1016/j.metabol.2014.10.025] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Revised: 10/21/2014] [Accepted: 10/23/2014] [Indexed: 02/09/2023]
Abstract
CONTEXT Anorexia nervosa (AN) is an excessive form of calorie restriction (CR) associated with pathological weight loss and alterations of the immune system. However, AN patients seem to be protected from common viral infections. OBJECTIVES To investigate the metabolic and molecular adaptations induced by sustained extreme CR in the peripheral blood mononuclear cells (PBMCs) of patients with restrictive alimentary AN. DESIGN Inflammatory cytokines and adipokines were measured in 15 young (age range, 15-24 years) AN female patients and 20 age-matched healthy controls. Isolated PBMCs were immunophenotyped by flow cytometry, and glycolysis and mitochondrial respiration were determined by measuring the extracellular acidification and oxygen consumption rate. Stress resistance to H2O2 and the antioxidant transcriptional profile of PBMCs and human fibroblasts incubated with sera from AN patients were also determined. RESULTS Compared with controls, AN patients (BMI, 15.9±0.4 kg/m(2)) had significantly fewer leucocytes, lymphocytes and NK cells, lower serum concentrations of leptin, IGF-1 and sTNFR1, and higher levels of adiponectin, sCD40L and sICAM-1 (p<0.05). IL-1β, TNFα, and IL-6 produced by PBMC cultured with autologous serum for 48 h were significantly lower in AN patients than in controls (p<0.01). Moreover, glycolysis and mitochondrial respiration were lower, and the antioxidant transcriptional profile was higher in the PBMCs of AN patients. Fibroblasts cultured in serum from AN patients showed a 24% increase in resistance to H2O2 damage. CONCLUSIONS Extreme CR in AN patients is associated with a reduction in several immune cell populations, but with higher antioxidant potential, stress resistance and an anti-inflammatory status.
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Affiliation(s)
- Daniela Omodei
- CEINGE-Biotecnologie Avanzate S.C.a R.L., via G. Salvatore 482, 80145 Napoli, Italy
| | - Valentina Pucino
- Dipartimento di Scienze Mediche Traslazionali, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy
| | - Giuseppe Labruna
- IRCCS Fondazione SDN, Istituto di Ricerca Diagnostica e Nucleare, 80143 Naples, Italy
| | - Claudio Procaccini
- Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy
| | - Mario Galgani
- Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy
| | - Francesco Perna
- Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy
| | - Daniele Pirozzi
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy
| | - Carmela De Caprio
- Centro Interuniversitario di Studi e Ricerche sull'Obesità (CISRO) e Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Napoli, Italy
| | - Gianni Marone
- Dipartimento di Scienze Mediche Traslazionali, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy
| | - Luigi Fontana
- CEINGE-Biotecnologie Avanzate S.C.a R.L., via G. Salvatore 482, 80145 Napoli, Italy; Dipartimento di Scienze Cliniche e Sperimentali, Università degli Studi di Brescia, 25123 Brescia, Italy; Division of Geriatrics and Nutritional Science, Washington University, St. Louis, MO, USA
| | - Franco Contaldo
- Centro Interuniversitario di Studi e Ricerche sull'Obesità (CISRO) e Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Napoli, Italy
| | - Fabrizio Pasanisi
- Centro Interuniversitario di Studi e Ricerche sull'Obesità (CISRO) e Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Napoli, Italy
| | - Giuseppe Matarese
- Dipartimento di Medicina e Chirurgia, Università di Salerno, Baronissi Campus, 84081 Salerno, Italy & IRCCS-MultiMedica, 20138 Milano, Italy
| | - Lucia Sacchetti
- CEINGE-Biotecnologie Avanzate S.C.a R.L., via G. Salvatore 482, 80145 Napoli, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy.
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Fisher L, Srikusalanukul W, Fisher A, Smith P. Liver function parameters in hip fracture patients: relations to age, adipokines, comorbidities and outcomes. Int J Med Sci 2015; 12:100-15. [PMID: 25589886 PMCID: PMC4293175 DOI: 10.7150/ijms.10696] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2014] [Accepted: 04/11/2014] [Indexed: 02/07/2023] Open
Abstract
AIM To asses liver markers in older patients with hip fracture (HF) in relation to age, comorbidities, metabolic characteristics and short-term outcomes. METHODS In 294 patients with HF (mean age 82.0±7.9 years, 72.1% women) serum alanine aminotransferase (ALT), gammaglutamyltransferase (GGT), alkaline phosphatase (ALP), albumin, bilirubin, 25(OH)vitaminD, PTH, calcium, phosphate, magnesium, adiponectin, leptin, resistin, thyroid function and cardiac troponin I were measured. RESULTS Elevated ALT, GGT, ALP or bilirubin levels on admission were observed in 1.7%-9.9% of patients. With age GGT, ALT and leptin decrease, while PTH and adiponectin concentrations increase. Higher GGT (>30 U/L, median level) was associated with coronary artery disease (CAD), diabetes mellitus (DM), and alcohol overuse; lower ALT (≤20 U/L, median level) with dementia; total bilirubin>20 μmol/L with CAD and alcohol overuse; and albumin>33 g/L with CAD. Multivariate adjusted regression analyses revealed ALT, ALP, adiponectin, alcohol overuse and DM as independent and significant determinants of GGT (as continuous or categorical variable); GGT for each other liver marker; and PTH for adiponectin. The risk of prolonged hospital stay (>20 days) was about two times higher in patients with GGT>30 U/L or adiponectin>17.14 ng/L (median level) and 4.7 times higher if both conditions coexisted. The risk of in-hospital death was 3 times higher if albumin was <33 g/L. CONCLUSIONS In older HF patients liver markers even within the normal range are associated with age-related disorders and outcomes. Adiponectin (but not 25(OH)vitaminD, PTH, leptin or resistin) is an independent contributor to higher GGT. Serum GGT and albumin predict prolonged hospital stay and in-hospital death, respectively. A unifying hypothesis of the findings presented.
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Affiliation(s)
- Leon Fisher
- 1. Department of Gastroenterology, The Canberra Hospital, Canberra, ACT, Australia
| | - Wichat Srikusalanukul
- 2. Department of Geriatric Medicine, The Canberra Hospital, Canberra, ACT, Australia
| | - Alexander Fisher
- 2. Department of Geriatric Medicine, The Canberra Hospital, Canberra, ACT, Australia ; 4. Australian National University Medical School, Canberra, ACT, Australia
| | - Paul Smith
- 3. Department of Orthopaedic Surgery, The Canberra Hospital, Canberra, ACT, Australia ; 4. Australian National University Medical School, Canberra, ACT, Australia
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Ma L, Feng M, Qian Y, Yang W, Liu J, Han R, Zhu H, Li Y. Insulin resistance is an important risk factor for cognitive impairment in elderly patients with primary hypertension. Yonsei Med J 2015; 56:89-94. [PMID: 25510751 PMCID: PMC4276782 DOI: 10.3349/ymj.2015.56.1.89] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
PURPOSE Insulin resistance plays a role in the development of dementia and hypertension. We investigated a possible relationship between cognitive impairment and insulin resistance in elderly Chinese patients with primary hypertension. MATERIALS AND METHODS One hundred and thirty-two hypertensive elderly patients (>60 years) were enrolled in this study, and assigned into either the cognitive impairment group (n=61) or the normal cognitive group (n=71). Gender, age, education, body mass index (BMI), waist hip ratio (WHR), total cholesterol (TC), triglyceride (TG), C-reactive protein (CRP), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), creatinine (Cr), fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model of assessment for insulin resistance index (HOMA-IR), systolic blood pressure, diastolic blood pressure, smoking history, atherosclerosis and the proportion of uncontrolled hypertension were compared between the two groups. Multi-factorial logistic regression analysis was performed. RESULTS No significant differences were found in gender, age, TC, CRP, HDL-C, LDL-C, Cr, BP, smoking history, atherosclerosis and the proportion of uncontrolled hypertension between the two groups. The cognitive impairment group had lower education levels, and higher BMI, WHR, TG, FPG, FINS, and HOMA-IR levels than the control group. Logistic regression analysis revealed the levels of education, BMI, WHR, and HOMA-IR as independent factors that predict cognitive impairment in patients. CONCLUSION Our study demonstrates that poor education and increased BMI, WHR, and HOMA-IR are independent risk factors for cognitive impairment in elderly patients with hypertension. Insulin resistance plays an important role in the development of cognitive impairment in primary elderly hypertensive patients.
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Affiliation(s)
- Lina Ma
- Department of Geriatrics, Xuan Wu Hospital, Capital Medical University, Beijing, China
| | - Ming Feng
- Department of Geriatrics, Xuan Wu Hospital, Capital Medical University, Beijing, China
| | - Yuying Qian
- Department of Geriatrics, Xuan Wu Hospital, Capital Medical University, Beijing, China
| | - Wei Yang
- Department of Geriatrics, Xuan Wu Hospital, Capital Medical University, Beijing, China
| | - Jia Liu
- Department of Geriatrics, Xuan Wu Hospital, Capital Medical University, Beijing, China
| | - Rui Han
- Department of Geriatrics, Xuan Wu Hospital, Capital Medical University, Beijing, China
| | - Hong Zhu
- Department of Geriatrics, Xuan Wu Hospital, Capital Medical University, Beijing, China
| | - Yun Li
- Department of Geriatrics, Xuan Wu Hospital, Capital Medical University, Beijing, China.
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Tavridou A, Georgoulidou A, Roumeliotis A, Roumeliotis S, Giannakopoulou E, Papanas N, Passadakis P, Manolopoulos VG, Vargemezis V. Association of Plasma Adiponectin and Oxidized Low-Density Lipoprotein with Carotid Intima-Media Thickness in Diabetic Nephropathy. J Diabetes Res 2015; 2015:507265. [PMID: 26064982 PMCID: PMC4443755 DOI: 10.1155/2015/507265] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Revised: 04/08/2015] [Accepted: 04/22/2015] [Indexed: 11/18/2022] Open
Abstract
AIMS We sought to determine the association between levels of adiponectin and oxidized low-density lipoprotein (ox-LDL) in patients with diabetic nephropathy as well as their effect on carotid intima-media thickness (cIMT). METHODS Adiponectin and ox-LDL were determined in 25 diabetic patients without nephropathy and 94 patients at different stages of diabetic nephropathy including subjects on hemodialysis. cIMT was measured using real-time B-mode ultrasonography. RESULTS Plasma adiponectin levels increased significantly with severity of diabetic nephropathy (P = 0.002), on the contrary to ox-LDL which decreased with disease severity (P < 0.001). cIMT was significantly higher at late stages of diabetic nephropathy compared with early stages (P = 0.022). Adiponectin was a significant negative predictor of ox-LDL levels (β = -5.45, P = 0.023), independently of confounding factors. There was no significant correlation between cIMT and adiponectin or ox-LDL either in the total sample population or according to disease staging. Cluster analysis showed that patients with the highest cIMT values, highest levels of adiponectin, and lowest levels of ox-LDL were included in one cluster and all assigned to stage 5 of diabetic nephropathy. CONCLUSIONS There was no significant association between adiponectin or ox-LDL and cIMT and, therefore, other factors affecting this surrogate marker of cardiovascular disease in diabetic nephropathy should be sought.
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Affiliation(s)
- Anna Tavridou
- Laboratory of Pharmacology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece
- *Anna Tavridou:
| | - Anastasia Georgoulidou
- Department of Nephrology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Athanasios Roumeliotis
- Department of Nephrology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Stefanos Roumeliotis
- Department of Nephrology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Efstathia Giannakopoulou
- Laboratory of Pharmacology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Nikolaos Papanas
- Second Department of Internal Medicine, Diabetes Clinic, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Ploumis Passadakis
- Department of Nephrology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Vangelis G. Manolopoulos
- Laboratory of Pharmacology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Vassilis Vargemezis
- Department of Nephrology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece
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Kumar J, Monica Lind P, Salihovic S, van Bavel B, Lind L, Ingelsson E. Influence of persistent organic pollutants on oxidative stress in population-based samples. CHEMOSPHERE 2014; 114:303-9. [PMID: 25113216 DOI: 10.1016/j.chemosphere.2014.05.013] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2014] [Revised: 04/29/2014] [Accepted: 05/02/2014] [Indexed: 05/20/2023]
Abstract
Persistent organic pollutants (POPs) are a large group of chemicals widely used and produced in various industrial applications. Many cell culture/animal studies have shown that POPs can induce oxidative stress. Since such data is lacking in humans, we conducted a large population-based study to analyze associations between POPs and oxidative stress markers. We measured following POPs; 16 polychlorinated biphenyls (PCBs), 5 organochlorine (OC) pesticides, octachlorinated dibenzo-p-dioxin, and polybrominated diphenyl ether 47, and oxidative stress markers; homocysteine, reduced [GSH] and oxidized glutathione [GSSG], glutathione ratio [GSSG/GSH], total glutathione, oxidized low-density lipoprotein [ox-LDL], ox-LDL antibodies, conjugated dienes, baseline conjugated dienes of LDL, and total anti-oxidative capacity in plasma samples collected from 992 70-year old individuals (50% women) from the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. Linear regression analyses were performed to study the associations between oxidative stress markers and summary measures of POPs including the total toxic equivalence (TEQ), sums of PCBs and OC pesticides (main exposures) while adjusting for potential confounders. In multivariable-adjusted analyses, sum of PCBs showed strong associations with ox-LDL (β=0.94; P=2.9*10(-6)). Further, sum of PCBs showed association with glutathione-related markers (GSSG: β=-0.01; P=6.0*10(-7); GSSG/GSH: β=-0.002; P=9.7*10(-10)), although in reverse direction. Other summary measures did not show any significant association with these markers. In our study of elderly individuals from the general population, we show that plasma levels of POPs are associated with markers of increased oxidative stress thereby suggesting that even low dose background exposure to POPs may be involved in oxidative stress.
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Affiliation(s)
- Jitender Kumar
- Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
| | - P Monica Lind
- Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden
| | - Samira Salihovic
- Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden
| | - Bert van Bavel
- MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden
| | - Lars Lind
- Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden
| | - Erik Ingelsson
- Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
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Allergic contact dermatitis is associated with significant oxidative stress. Dermatol Res Pract 2014; 2014:415638. [PMID: 25183967 PMCID: PMC4144152 DOI: 10.1155/2014/415638] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2014] [Accepted: 07/23/2014] [Indexed: 11/17/2022] Open
Abstract
Background. Research has confirmed the involvement of oxidative stress (OxS) in allergic contact dermatitis whilst other inflammation-related biomarkers have been less studied. Objective. To evaluate systemic levels of selected inflammatory markers, OxS indices and adipokines as well as their associations in allergic contact dermatitis. Methods. In 40 patients, interleukin- (IL-) 6, monocyte chemoattractant protein (MCP-1), and IL-10 levels were measured in sera with the Evidence Investigator Cytokine & Growth factors High-Sensitivity Array, total peroxide concentration (TPX) and total antioxidant capacity (TAC) by means of spectrophotometry, and the plasma concentrations of adiponectin and leptin by the quantitative sandwich enzyme immunoassay technique. Results. TNF-α level (P < 0.01) and TPX (P < 0.0001) were increased whilst IL-10 (P < 0.05) and TAC (P < 0.0001) were decreased in the patients as compared to controls. Correlation and multiple linear regression analysis identified both, TPX and TAC (inversely), as possible independent markers for evaluating allergic contact dermatitis. Adiponectin level in patients was increased (P < 0.0001), but neither adiponectin nor leptin correlated significantly with the biomarkers of inflammation or OxS. Conclusion. OxS parameters, especially TPX and OSI, reflect the degree of systemic inflammation associated with allergic contact dermatitis in the best way. The relation between OxS and adiponectin level warrants further studies.
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Morimoto HK, Simão ANC, de Almeida ERD, Ueda LT, Oliveira SR, de Oliveira NB, Petenucci DL, Panis C, Cecchini R, Dichi I, Reiche EMV. Role of metabolic syndrome and antiretroviral therapy in adiponectin levels and oxidative stress in HIV-1 infected patients. Nutrition 2014; 30:1324-30. [PMID: 25280407 DOI: 10.1016/j.nut.2014.03.017] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2013] [Revised: 02/10/2014] [Accepted: 03/17/2014] [Indexed: 01/08/2023]
Abstract
OBJECTIVE HIV-1 infection is accompanied by severe metabolic and immune dysfunction. The aim of this study was to evaluate the role of metabolic syndrome (MetS) and antiretroviral therapy (ART) utilization on the adiponectin levels and oxidative stress in patients infected with HIV-1. METHODS We allocated 285 patients into four groups: group 1: patients without MetS who were not using ART; group 2: patients without MetS using ART; group 3: patients with MetS who were not using ART; and group 4: patients with MetS using ART. Biochemical, immunologic, and oxidative stress parameters were measured. RESULTS Group 4 exhibited higher lipoperoxides when compared with group 1 (P < 0.0001) and higher advanced oxidation protein products (AOPP) compared with group 2 or group 1 (P < 0.0001). Group 3 also presented higher AOPP than group 2 (P < 0.05). Group 4 showed lower adiponectin levels compared with groups 1 or 2 (P < 0.0001). Similarly, group 3 presented lower adiponectin levels compared with group 2 (P < 0.05) or group 1 (P < 0.0001). Multivariate analysis showed that both an increase in AOPP and a decrease in total radical-trapping antioxidant parameter/uric acid were independently associated with MetS in HIV-1 patients. Regarding immunologic markers of HIV-1 disease progression and viral replication, group 4 exhibited significantly higher CD45(+), CD3(+), and CD4(+) T cells count compared with group 2 (P < 0.01). CONCLUSION HIV-1-infected patients with MetS exhibited hypoadiponectinemia and increased oxidative stress, and these findings were not influenced by ART use. The findings of the present study allow the suggestion that MetS and inflammation might be mainly responsible for the aforementioned features. More studies are needed to verify whether drugs or food, which yield increased adiponectinemia and decreased oxidative stress, could reduce cardiovascular risk in HIV-infected patients.
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Affiliation(s)
- Helena K Morimoto
- Department of Pathology, Clinical Analysis and Toxicology, University of Londrina, Londrina, Paraná, Brazil
| | - Andréa N C Simão
- Department of Pathology, Clinical Analysis and Toxicology, University of Londrina, Londrina, Paraná, Brazil.
| | - Elaine R D de Almeida
- Department of Pathology, Clinical Analysis and Toxicology, University of Londrina, Londrina, Paraná, Brazil
| | - Luiz T Ueda
- Integrated Center of Infectious Diseases, Secretariat Health of Paraná State, Londrina, Paraná, Brazil
| | - Sayonara R Oliveira
- Department of Pathology, Clinical Analysis and Toxicology, University of Londrina, Londrina, Paraná, Brazil
| | - Natalia B de Oliveira
- Department of Pathology, Clinical Analysis and Toxicology, University of Londrina, Londrina, Paraná, Brazil
| | - Diego L Petenucci
- Department of Pathology, Clinical Analysis and Toxicology, University of Londrina, Londrina, Paraná, Brazil
| | - Carolina Panis
- Laboratory of Pathophysiology of Free Radicals, University of Londrina, Londrina, Paraná, Brazil
| | - Rubens Cecchini
- Laboratory of Pathophysiology of Free Radicals, University of Londrina, Londrina, Paraná, Brazil
| | - Isaias Dichi
- Department of Internal Medicine, University of Londrina, Londrina, Paraná, Brazil
| | - Edna M V Reiche
- Department of Pathology, Clinical Analysis and Toxicology, University of Londrina, Londrina, Paraná, Brazil
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Sen S, Iyer C, Meydani SN. Obesity during pregnancy alters maternal oxidant balance and micronutrient status. J Perinatol 2014; 34:105-11. [PMID: 24355940 DOI: 10.1038/jp.2013.153] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2013] [Revised: 10/28/2013] [Accepted: 11/12/2013] [Indexed: 01/05/2023]
Abstract
OBJECTIVE Little is known about the effect of obesity on inflammatory status in pregnant women. The objective of this study was to determine the effect of obesity on markers of inflammation, oxidative stress and micronutrient status in obese pregnant women and their infants compared with lean controls (Lc). STUDY DESIGN This was a prospective case-control study. A total of 15 obese (Ob; body mass index (BMI) >30 kg m(-2)) and 15 lean (BMI 18-25 kg m(-2)) women were recruited based on prepregnancy BMI. Vitamins A, B6, C, E and 25-hydroxyvitamin D (25(OH)D), zinc, red blood cell (RBC) folate, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α and oxidized and reduced glutathione were measured from maternal blood between 24 and 28 weeks of gestation. Vitamins A, B6, C and E, 25(OH)D, zinc, red blood cell folate, CRP and IL-6 were measured from cord blood at delivery. RESULT Ob pregnant women have statistically significantly lower levels of vitamin B6, vitamin C, vitamin E, RBC folate, higher CRP and IL-6 levels and higher ratio of oxidized to reduced glutathione compared with Lc pregnant women. Infants born to Ob mothers did not have statistically significantly higher measures of inflammation or oxidative stress. There were no differences in micronutrient concentrations between Lc and Ob infants, but folate, vitamin B6 and zinc levels correlated strongly between mother and infant. There was no statistically significant difference in any parameter between Ob and Lc cord blood. CONCLUSION Ob pregnant women have increased inflammation and oxidative stress, and lower levels of nutritional antioxidant defenses compared with Lc pregnant women. We speculate that lower antioxidant defenses combined with increased oxidative stress and inflammation may contribute to the adverse outcomes associated with pregnancy in Ob women.
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Affiliation(s)
- S Sen
- 1] Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA [2] Mother Infant Research Institute, Tufts Medical Center, Boston, MA, USA [3] Division of Newborn Medicine, Department of Pediatrics, Tufts Medical Center, Boston, MA, USA
| | - C Iyer
- Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, MA, USA
| | - S N Meydani
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
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Del Ben M, Polimeni L, Baratta F, Bartimoccia S, Carnevale R, Loffredo L, Pignatelli P, Violi F, Angelico F. Serum Cytokeratin-18 Is Associated with NOX2-Generated Oxidative Stress in Patients with Nonalcoholic Fatty Liver. Int J Hepatol 2014; 2014:784985. [PMID: 24678423 PMCID: PMC3941779 DOI: 10.1155/2014/784985] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2013] [Accepted: 12/04/2013] [Indexed: 12/17/2022] Open
Abstract
Background & Aims. Hepatocyte apoptosis may play a role in progression of nonalcoholic fatty liver and oxidative stress seems one of the key mechanisms responsible for liver damage. The aim was to determine the association of oxidative stress with cytokeratin-18 M30 fragment levels, a marker of hepatocyte apoptosis. Methods. Steatosis severity was defined according to Hamaguchi's echographic criteria in 209 patients with nonalcoholic fatty liver. Serum cytokeratin-18, urinary 8-iso-prostaglandin F2 α , soluble NOX2-derived peptide, and adiponectin were measured. Results. Serum cytokeratin-18 progressively increased with steatosis severity (from 169.5 (129.3/183.8) to 176 (140/190) and 180 (169.5/192.5) μ IU/mL in mild, moderate, and severe steatosis, respectively; P < 0.01). After stratification by cytokeratin-18 tertiles, a significant progression of body mass index, HOMA-IR, triglycerides, urinary 8-iso-PGF2 α , soluble NOX2-derived peptide, and of the prevalence of diabetes and severe steatosis was found, while HDL-cholesterol and adiponectin progressively decreased. A positive correlation between cytokeratin-18 and body mass index, HOMA-IR, Hamaguchi's score, urinary 8-iso-PGF2 α , and soluble NOX2-derived peptide and a negative correlation between cytokeratin-18 and HDL-cholesterol and adiponectin were found. Body mass index, adiponectin, and soluble NOX2-derived peptide were independent predictors of serum cytokeratin-18 levels (adjusted R (2) = 0.36). Conclusion. We support an association between oxidative stress and severity of liver damage in patients with nonalcoholic fatty liver.
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Affiliation(s)
- M. Del Ben
- Department of Internal Medicine and Medical Specialities, Sapienza University, Rome, Italy
| | - L. Polimeni
- Department of Internal Medicine and Medical Specialities, Sapienza University, Rome, Italy
| | - F. Baratta
- Department of Internal Medicine and Medical Specialities, Sapienza University, Rome, Italy
| | - S. Bartimoccia
- Department of Internal Medicine and Medical Specialities, Sapienza University, Rome, Italy
| | - R. Carnevale
- Department of Internal Medicine and Medical Specialities, Sapienza University, Rome, Italy
| | - L. Loffredo
- Department of Internal Medicine and Medical Specialities, Sapienza University, Rome, Italy
| | - P. Pignatelli
- Department of Internal Medicine and Medical Specialities, Sapienza University, Rome, Italy
| | - F. Violi
- Department of Internal Medicine and Medical Specialities, Sapienza University, Rome, Italy
| | - F. Angelico
- Department of Internal Medicine and Medical Specialities, Sapienza University, Rome, Italy
- Department of Public Health and Infectious Disease, Sapienza University, Rome, Italy
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