Obesity

Oxidative Stress and Dietary Antioxidants

Amelia Marti del Moral, Concepcion M. Aguilera

• Publisher: Academic Press
• Year: 2018
• Print ISBN: 9780128125045
• eBook ISBN: 9780128125052
• Topic: Medicine
• Subtopic: Endocrinology & Metabolism

Obesity: Oxidative Stress and Dietary Antioxidants cover the science of oxidative stress in obesity and associated conditions, including metabolic syndrome, bariatric surgery, and the potentially therapeutic usage of natural antioxidants in the diet or food matrix. The processes within the science of oxidative stress are not described in isolation, but in concert with other processes, such as apoptosis, cell signaling and receptor mediated responses. This approach recognizes that diseases are often multifactorial and oxidative stress is but a single component. The book is designed for nutritionists, dietitians, food scientists, physicians and clinical workers, health care workers and research scientists.- Covers the basic processes of oxidative stress, from molecular biology, to whole organs- Highlights antioxidants in foods, including plants and other components of diet- Provides the framework for further, in-depth analysis or studies via well-designed clinical trials or via the analysis of pathways, mechanisms and componentsa

Chapter 1

Oxidative Stress and Inflammation in Obesity and Metabolic Syndrome

Francisco J. Ruiz-Ojeda¹, Josune Olza^1,2,3, Ángel Gil^1,2,3, and Concepción M. Aguilera^{1,2,3 1}University of Granada, Granada, Spain ²IBS (Instituto de Investigación Biosanitaria de Granada), Granada, Spain ³CIBERobn (Centro de Investigación Biomédica en Red, Fisiopatología de la obesidad y nutrición), Carlos III Health Institute, Madrid, Spain

Abstract

Obesity is a worldwide public health problem that has been increasing in the last decades. It is characterized by excessive fat accumulation, and accompanied by low-grade chronic inflammation and increased oxidative stress. A growing body of evidence supports that both chronic inflammation and oxidative stress play a key role in the development of obesity-associated comorbidities such as insulin resistance (IR), which probably is the first step of a dysfunctional metabolic system. Subsequent to central obesity, IR, hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, hypertension, and fatty liver are grouped in the so-called metabolic syndrome (MetS). The purpose of this chapter is to review the clinical correlates of systemic oxidative stress and inflammation markers in patients with obesity or MetS.

Keywords

Adipose tissue; Inflammation; Insulin resistance; Metabolic syndrome; Obesity; Oxidative stress

1. Introduction

Obesity is a worldwide public health problem that has been increasing in the last decades. According to the World Health Organization, obesity and overweight are defined as “abnormal or excessive fat accumulation that may impair health.” Increased consumption of highly caloric foods, without an equal increase in energy expenditure, mainly by physical activity, leads to an unhealthy increase in weight; decreased levels of physical activity will result in an energy imbalance and will lead to weight gain. Worldwide obesity has more than doubled since 1980. In 2014, more than 1.9 billion adults 18 years and older were overweight, and of these over 600 million were obese. Thus 30% of adults aged 18 years and over were overweight in 2014 and 13% were obese. In addition, 41 million children under the age of five were overweight or obese in 2014. Thus the problem is twice as important than in the 1980s, and about 13% of the population is estimated to be obese [1].

Obesity is a well-known risk factor for insulin resistance (IR) and the development of type 2 diabetes (T2D). Diabetes is associated with complications such as cardiovascular diseases (CVDs), nonalcoholic fatty liver disease (NAFLD), retinopathy, angiopathy, and nephropathy, which consequently lead to higher mortality risks. Obesity-associated diabetes is hence a major public health problem, and paucity of available medication against IR requires the validation of new therapeutic targets [2]. Deaths from CVD and diabetes accounted for approximately 65% of all deaths, and general adiposity and mainly abdominal adiposity are associated with increased risk of death for all these disorders. Adiposity is also associated with a state of low-grade chronic inflammation, with increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 releases, which interfere with adipose cell differentiation and the action pattern of adiponectin and leptin until the adipose tissue (AT) begins to be dysfunctional. Accordingly, the subjects present IR and hyperinsulinemia, probably the first step of a dysfunctional metabolic system. Subsequent to central obesity, IR, hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, hypertension, and fatty liver are grouped in the so-called metabolic syndrome (MetS) [3]. With regard to MetS, overnutrition leads to Kuppfer cell activation, chronic inflammation, hepatic steatosis, and eventual steatohepatitis and cirrhosis. Similarly, in the vascular intima, overnutrition-induced hyperlipidemia leads to oxidized low-density lipoprotein (LDL) formation and uptake in macrophages leading to foam cell formation and vascular inflammation. The cross-talk between metabolism and inflammation is also demonstrated by immunomodulatory corticosteroids that also have strong effects on host protein and carbohydrate metabolism [4].

In subjects with MetS an energy balance is critical to maintain a healthy body weight, mainly limiting high energy density foods. The first factor to be avoided in the prevention of MetS is obesity; the percentage of fat in the diet has traditionally been associated with the development of obesity. However, it is well established that the type of fat consumed could be more decisive than the total amount of fat consumed when we only look at changes in body composition and distribution of AT. Additionally, IR is a feature of MetS and is associated with other components of the syndrome. The beneficial impact of fat quality on insulin sensitivity (IS) was not seen in individuals with a high fat intake (>37% of energy). Other dietary factors that can influence various components of MetS, like postprandial glycemic and insulin levels, triacylglycerols (TAGs) and high-density lipoprotein (HDL) cholesterol levels, weight regulation and body composition, as well as fatty liver, are the glycemic load and the excess of fructose, and amount of dietary fiber content of food eaten. The increased levels of TAG associated with hypoalphalipoproteinemia are a feature of IR and MetS, and increase cardiovascular risk regardless of LDL cholesterol levels [3,4].

AT is the main organ for energy storage, but also AT itself can be seen as an endocrine organ that plays a critical role in immune homeostasis. In healthy people, AT represents about 20% of the body mass in men and about 30% in women. In obesity, it expands tremendously and may constitute more than 50% of the body mass in morbidly obese individuals. AT produces and releases a variety of adipokines and cytokines, including leptin, adiponectin, resistin, and visfatin, as well as TNF-α and IL-6, among others [5]. Proinflammatory molecules produced by AT have been implicated as active participants in the development of metabolic disease. Furthermore, AT macrophages (ATMs) are prominent sources of proinflammatory cytokines, which can block insulin action in AT, skeletal muscle, and liver autocrine/paracrine signaling and cause systemic IR via endocrine signaling, providing a potential link between inflammation and IR [6].

2. Oxidative Stress, Obesity, and Metabolic Syndrome

Another critical factor that is involved in the pathogenesis of metabolic diseases is oxidative stress. Oxidative stress is a state of imbalance between the oxidative and antioxidative systems of cells and tissues, resulting in the production of excessive oxidative free radicals and reactive oxygen species (ROS) [7] caused either by exposure to damaging agents, or limited capabilities of endogenous antioxidant systems [8]. The components of the MetS as well as their comorbidities lead to the progression of prooxidative status contributing to the damage of biomolecules that are highly reactive and can stimulate cell and tissue dysfunctions, leading to the development of metabolic diseases [7]. High levels of circulating glucose and lipids can result in excessive energy substrates for metabolic pathways in adipose and nonadipose cells, increasing the production of ROS; if ROS are not well controlled, they can damage proteins, lipids, sugars, and DNA [8,9].

It is well known that mitochondria are the most critical sites for ROS production, because an excess supply of electrons to the electron transport chain can produce very high levels of ROS [10]. In addition to the range of pathologies that it can cause, this increase in ROS production can also damage the mitochondria, affecting the cellular redox signaling, indicating that this organelle can be an important target in the treatment of those pathologies [11].

A large quantity of epidemiological as well as in vivo and in vitro studies have suggested that obesity and redox alteration are interconnected through mutual mechanisms. It is hypothesized that oxidative stress is one of the links between fat accumulation-derived alterations and the appearance of a cluster of health problems including adipokine secretion alteration, inflammation, and IR (Fig. 1.1).

ROS have been involved in the adipogenesis (proliferation and differentiation) process, indicating its participation in the development of metabolic diseases through various mechanisms including chronic adipocyte inflammation, fatty acid oxidation, overconsumption of oxygen and accumulation of cellular damage, diet, and mitochondrial activity. Obesity can cause oxidative stress through the activation of intracellular pathways such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), oxidative phosphorylation in mitochondria, glycoxidation, protein kinase C, and polyol [12]; it can also deregulate the synthesis of adipokines such as adiponectin, visfatin, resistin, leptin, plasminogen activator inhibitor-1 (PAI-1), and TNF-α and IL-6. Both TNF-α and IL-6 increase the activity of NOX and the production of superoxide anions [13]. Indeed it seems that obesity is the connection between oxidative stress and inflammation although it is not easy to confirm which one antecedes the other. It has also been observed that ox...

Table of contents

• Cover image
• Title page
• Table of Contents
• Related Titles
• Copyright
• List of Contributors
• About the Editors
• Preface
• Chapter 1. Oxidative Stress and Inflammation in Obesity and Metabolic Syndrome
• Chapter 2. Genetics of Oxidative Stress and Obesity-Related Diseases
• Chapter 3. Molecular Basis of Oxidative Stress and Inflammation
• Chapter 4. Inflammation and Oxidative Stress in Adipose Tissue: Nutritional Regulation
• Chapter 5. Vascular Damage in Metabolic Disorders: Role of Oxidative Stress
• Chapter 6. Obesity and Nonalcoholic Fatty Liver Disease: Role of Oxidative Stress
• Chapter 7. Kidney Damage in Obese Subjects: Oxidative Stress and Inflammation
• Chapter 8. Inflammatory and Oxidative Stress Markers in Skeletal Muscle of Obese Subjects
• Chapter 9. Evaluation of Oxidative Stress in Humans: A Critical Point of View
• Chapter 10. Benefits of Selenium, Magnesium, and Zinc in Obesity and Metabolic Syndrome
• Chapter 11. Polyphenols in Obesity and Metabolic Syndrome
• Chapter 12. Aging, Telomere Integrity, and Antioxidant Food
• Chapter 13. Antioxidant Supplements in Obesity and Metabolic Syndrome: Angels or Demons
• Index