Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies.
TL;DR: The aspects of metabolic disorders-induced oxidative stress in major pathological conditions and strategies for their prevention and therapy are discussed.
About: This article is published in Life Sciences.The article was published on 2016-03-01. It has received 717 citations till now. The article focuses on the topics: Oxidative stress & Metabolic disorder.
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TL;DR: The mechanisms of actions of COS have been found to involve the modulation of several important pathways including the suppression of nuclear factor kappa B and mitogen‐activated protein kinases (MAPK and the activation of AMP‐activatedprotein kinase (AMPK).
341 citations
Cites background from "Oxidative stress and metabolic diso..."
...Oxidative stress plays pivotal roles in the pathogenesis of several diseases, especially age-related disorders including diabetes mellitus, hypertension and cancer (Cerda et al., 2014; Rani et al., 2016)....
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TL;DR: It is suggested that the diet-related key changes in the developmental process include an increased production of reactive oxygen species and oxidative stress, development of hyperinsulinemia and insulin resistance, low-grade inflammation and an abnormal activation of the sympathetic nervous system and the renin-angiotensin system, all of which play pivotal roles in the development of diseases of civilization.
Abstract: Westernized populations are plagued by a plethora of chronic non-infectious degenerative diseases, termed as "civilization diseases", like obesity, diabetes, cardiovascular diseases, cancer, autoimmune diseases, Alzheimer's disease and many more, diseases which are rare or virtually absent in hunter-gatherers and other non-westernized populations. There is a growing awareness that the cause of this amazing discrepancy lies in the profound changes in diet and lifestyle during recent human history. This paper shows that the transition from Paleolithic nutrition to Western diets, along with lack of corresponding genetic adaptations, cause significant distortions of the fine-tuned metabolism that has evolved over millions of years of human evolution in adaptation to Paleolithic diets. With the increasing spread of Western diet and lifestyle worldwide, overweight and civilization diseases are also rapidly increasing in developing countries. It is suggested that the diet-related key changes in the developmental process include an increased production of reactive oxygen species and oxidative stress, development of hyperinsulinemia and insulin resistance, low-grade inflammation and an abnormal activation of the sympathetic nervous system and the renin-angiotensin system, all of which play pivotal roles in the development of diseases of civilization. In addition, diet-related epigenetic changes and fetal programming play an important role. The suggested pathomechanism is also able to explain the well-known but not completely understood close relationship between obesity and the wide range of comorbidities, like type 2 diabetes mellitus, cardiovascular disease, etc., as diseases of the same etiopathology. Changing our lifestyle in accordance with our genetic makeup, including diet and physical activity, may help prevent or limit the development of these diseases.
322 citations
TL;DR: The aim of this review was to provide a theoretical basis and relevant references, which may lead to the improvement of the sensitivity of radiotherapy and prolong the survival of cancer patients.
Abstract: Radioresistance is a major factor leading to the failure of radiotherapy and poor prognosis in tumor patients. Following the application of radiotherapy, the activity of various metabolic pathways considerably changes, which may result in the development of resistance to radiation. Here, we discussed the relationships between radioresistance and mitochondrial and glucose metabolic pathways, aiming to elucidate the interplay between the tumor cell metabolism and radiotherapy resistance. In this review, we additionally summarized the potential therapeutic targets in the metabolic pathways. The aim of this review was to provide a theoretical basis and relevant references, which may lead to the improvement of the sensitivity of radiotherapy and prolong the survival of cancer patients.
258 citations
TL;DR: An overview of concepts and their potential inter-relationships in the development of insulin resistance, with particular regard to changes in adipose organ and skeletal muscle is provided.
Abstract: Obesity is a major health risk factor, and obesity-induced morbidity and complications account for huge costs for affected individuals, families, healthcare systems, and society at large In particular, obesity is strongly associated with the development of insulin resistance, which in turn plays a key role in the pathogenesis of obesity-associated cardiometabolic complications, including metabolic syndrome components, type 2 diabetes, and cardiovascular diseases Insulin sensitive tissues, including adipose tissue, skeletal muscle, and liver, are profoundly affected by obesity both at biomolecular and functional levels Altered adipose organ function may play a fundamental pathogenetic role once fat accumulation has ensued Modulation of insulin sensitivity appears to be, at least in part, related to changes in redox balance and oxidative stress as well as inflammation, with a relevant underlying role for mitochondrial dysfunction that may exacerbate these alterations Nutrients and substrates as well as systems involved in host-nutrient interactions, including gut microbiota, have been also identified as modulators of metabolic pathways controlling insulin action This review aims at providing an overview of these concepts and their potential inter-relationships in the development of insulin resistance, with particular regard to changes in adipose organ and skeletal muscle
204 citations
TL;DR: It is shown that existing regulatory processes are more than adequate to limit the toxicity of iron even in response to iron overload and that intracellular iron is not toxic but a stress responsive programmed cell death-inducing second messenger.
190 citations
References
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University of Washington1, Sapienza University of Rome2, Mekelle University3, University of Texas at San Antonio4, King Saud bin Abdulaziz University for Health Sciences5, Debre markos University6, Emory University7, University of Oxford8, University of Cartagena9, United Nations Population Fund10, University of Birmingham11, Stanford University12, Aga Khan University13, University of Melbourne14, National Taiwan University15, University of Cambridge16, University of California, San Diego17, Public Health Foundation of India18, Public Health England19, University of Peradeniya20, Harvard University21, National Institutes of Health22, Tehran University of Medical Sciences23, Auckland University of Technology24, University of Sheffield25, University of Western Australia26, Karolinska Institutet27, Birzeit University28, Brandeis University29, American Cancer Society30, Ochsner Medical Center31, Yonsei University32, University of Bristol33, Heidelberg University34, Vanderbilt University35, South African Medical Research Council36, Jordan University of Science and Technology37, New Generation University College38, Northeastern University39, Simmons College40, Norwegian Institute of Public Health41, Boston University42, Chinese Center for Disease Control and Prevention43, University of Bari44, University of São Paulo45, University of Otago46, University of Crete47, International Centre for Diarrhoeal Disease Research, Bangladesh48, Fred Hutchinson Cancer Research Center49, Teikyo University50, Bhabha Atomic Research Centre51, University of Tokyo52, Finnish Institute of Occupational Health53, Heriot-Watt University54, University of Alabama at Birmingham55, Griffith University56, National Center for Disease Control and Public Health57, University of California, Irvine58, Johns Hopkins University59, New York University60, University of Queensland61, Universidade Federal de Minas Gerais62, National Research University – Higher School of Economics63, University of Bergen64, Columbia University65, Shandong University66, University of North Carolina at Chapel Hill67, Fujita Health University68, Korea University69, Chongqing Medical University70, Zhejiang University71
TL;DR: The global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013 is estimated using a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs).
9,180 citations
TL;DR: Dysfunction of the immune response and metabolic regulation interface can be viewed as a central homeostatic mechanism, dysfunction of which can lead to a cluster of chronic metabolic disorders, particularly obesity, type 2 diabetes and cardiovascular disease.
Abstract: Metabolic and immune systems are among the most fundamental requirements for survival. Many metabolic and immune response pathways or nutrient- and pathogen-sensing systems have been evolutionarily conserved throughout species. As a result, immune response and metabolic regulation are highly integrated and the proper function of each is dependent on the other. This interface can be viewed as a central homeostatic mechanism, dysfunction of which can lead to a cluster of chronic metabolic disorders, particularly obesity, type 2 diabetes and cardiovascular disease. Collectively, these diseases constitute the greatest current threat to global human health and welfare.
7,536 citations
"Oxidative stress and metabolic diso..." refers background in this paper
...Also, high glucose-induced oxidative stress promotes inflammatory condition by modulating the expression of various cytokines such as TNF-α, IL-6, IL-1β, and IL-18 which further act as autocrine/paracrine agonists and trigger hypertrophy-mediated myocardial remodelling leading to cardiovascular diseases [115, 116], which establishes the fact that there is a close association between metabolic disorders and oxidative stress which instigates mechanisms of cardiac insult....
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TL;DR: Current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women, and increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites.
Abstract: background The influence of excess body weight on the risk of death from cancer has not been fully characterized. methods In a prospectively studied population of more than 900,000 U.S. adults (404,576 men and 495,477 women) who were free of cancer at enrollment in 1982, there were 57,145 deaths from cancer during 16 years of follow-up. We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites, while controlling for other risk factors in multivariate proportional-hazards models. We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population. results The heaviest members of this cohort (those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of at least 40) had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. For men, the relative risk of death was 1.52 (95 percent confidence interval, 1.13 to 2.05); for women, the relative risk was 1.62 (95 percent confidence interval, 1.40 to 1.87). In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin’s lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. On the basis of associations observed in this study, we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women. conclusions Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites.
7,095 citations
TL;DR: These results from a representative sample of US adults show that the metabolic syndrome is highly prevalent and the large numbers of US residents with the metabolic Syndrome may have important implications for the health care sector.
Abstract: ContextThe Third Report of the National Cholesterol Education Program Expert
Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in
Adults (ATP III) highlights the importance of treating patients with the metabolic
syndrome to prevent cardiovascular disease. Limited information is available
about the prevalence of the metabolic syndrome in the United States, however.ObjectiveTo estimate the prevalence of the metabolic syndrome in the United States
as defined by the ATP III report.Design, Setting, and ParticipantsAnalysis of data on 8814 men and women aged 20 years or older from the
Third National Health and Nutrition Examination Survey (1988-1994), a cross-sectional
health survey of a nationally representative sample of the noninstitutionalized
civilian US population.Main Outcome MeasuresPrevalence of the metabolic syndrome as defined by ATP III (≥3 of
the following abnormalities): waist circumference greater than 102 cm in men
and 88 cm in women; serum triglycerides level of at least 150 mg/dL (1.69
mmol/L); high-density lipoprotein cholesterol level of less than 40 mg/dL
(1.04 mmol/L) in men and 50 mg/dL (1.29 mmol/L) in women; blood pressure of
at least 130/85 mm Hg; or serum glucose level of at least 110 mg/dL (6.1 mmol/L).ResultsThe unadjusted and age-adjusted prevalences of the metabolic syndrome
were 21.8% and 23.7%, respectively. The prevalence increased from 6.7% among
participants aged 20 through 29 years to 43.5% and 42.0% for participants
aged 60 through 69 years and aged at least 70 years, respectively. Mexican
Americans had the highest age-adjusted prevalence of the metabolic syndrome
(31.9%). The age-adjusted prevalence was similar for men (24.0%) and women
(23.4%). However, among African Americans, women had about a 57% higher prevalence
than men did and among Mexican Americans, women had about a 26% higher prevalence
than men did. Using 2000 census data, about 47 million US residents have the
metabolic syndrome.ConclusionsThese results from a representative sample of US adults show that the
metabolic syndrome is highly prevalent. The large numbers of US residents
with the metabolic syndrome may have important implications for the health
care sector.
6,961 citations
"Oxidative stress and metabolic diso..." refers background in this paper
...noma [5], whereas diabetes is reported to predict mortality from cancer of the colon, pancreas, female breast, male liver and bladder [6]....
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TL;DR: The description outlined here facilitates the understanding of factors that favour mitochondrial ROS production and develops better methods to measure mitochondrial O2•− and H2O2 formation in vivo, as uncertainty about these values hampers studies on the role of mitochondrial ROS in pathological oxidative damage and redox signalling.
Abstract: The production of ROS (reactive oxygen species) by mammalian mitochondria is important because it underlies oxidative damage in many pathologies and contributes to retrograde redox signalling from the organelle to the cytosol and nucleus. Superoxide (O2•−) is the proximal mitochondrial ROS, and in the present review I outline the principles that govern O2•− production within the matrix of mammalian mitochondria. The flux of O2•− is related to the concentration of potential electron donors, the local concentration of O2 and the second-order rate constants for the reactions between them. Two modes of operation by isolated mitochondria result in significant O2•− production, predominantly from complex I: (i) when the mitochondria are not making ATP and consequently have a high Δp (protonmotive force) and a reduced CoQ (coenzyme Q) pool; and (ii) when there is a high NADH/NAD+ ratio in the mitochondrial matrix. For mitochondria that are actively making ATP, and consequently have a lower Δp and NADH/NAD+ ratio, the extent of O2•− production is far lower. The generation of O2•− within the mitochondrial matrix depends critically on Δp, the NADH/NAD+ and CoQH2/CoQ ratios and the local O2 concentration, which are all highly variable and difficult to measure in vivo. Consequently, it is not possible to estimate O2•− generation by mitochondria in vivo from O2•−-production rates by isolated mitochondria, and such extrapolations in the literature are misleading. Even so, the description outlined here facilitates the understanding of factors that favour mitochondrial ROS production. There is a clear need to develop better methods to measure mitochondrial O2•− and H2O2 formation in vivo, as uncertainty about these values hampers studies on the role of mitochondrial ROS in pathological oxidative damage and redox signalling.
6,371 citations