Elsevier

Translational Research

Volume 158, Issue 6, December 2011, Pages 369-384
Translational Research

Review Article
Oxidant mechanisms in childhood obesity: the link between inflammation and oxidative stress

https://doi.org/10.1016/j.trsl.2011.08.004Get rights and content

Evidence of obesity-induced oxidative stress in adults has emerged in the past several years, and similar evidence has been demonstrated in children more recently. The reactive species of oxygen or nitrogen can chemically alter all major classes of biomolecules by modifying their structure and function. Organisms have developed mechanisms to protect biomolecules from the deleterious effects of free radicals. These include the enzymes superoxide dismutase, catalase, and glutathione peroxidase, as well as water and lipid-soluble antioxidants, such as glutathione, ascorbate (vitamin C), α-tocopherol (vitamin E), and β-carotene. Obesity creates oxidant conditions that favor the development of comorbid diseases. Energy imbalances lead to the storage of excess energy in adipocytes, resulting in both hypertrophy and hyperplasia. These processes are associated with abnormalities of adipocyte function, particularly mitochondrial stress and disrupted endoplasmic reticulum function. In this sense, oxidative stress can also be induced by adipocyte associated inflammatory macrophages. There is a close link among obesity, a state of chronic low-level inflammation, and oxidative stress. In addition, the dysregulation of adipocytokines, which are secreted by adipose tissue and promoted by oxidative stress, act synergistically in obesity-related metabolic abnormalities. Adipocytokines link the local and systemic inflammation responses in the context of obesity. It is thought that the evaluation of oxidative status may allow for the identification of patients at an increased risk of complications. Decreasing the levels of chronic inflammation and oxidative stress in childhood may decrease cardiovascular morbidity and mortality in adulthood.

Section snippets

Oxidative Stress

Oxidative stress is generally described as an imbalance in net levels of reactive oxygen species (ROS) relative to the body's antioxidant capacity, resulting in the accumulation of oxidative products. This imbalance leads to cellular dysregulation, which alters cell signaling and other cellular functions.9 Oxidative stress has been implicated in various types of pathogenic processes, including degenerative diseases, atherosclerosis and inflammation.10

ROS include free radicals, such as

Mechanisms of Free Radical Formation in Obesity

The production of ROS and RNS can occur at the cellular level in response to diverse stimuli, such as the metabolic overload caused by an overabundance of macronutrients. The primary determinants for ROS or RNS generation are the family of nicotinamide adenine dinucleotide phosphate oxidases (NOX), mitochondrial respiration, endoplasmic reticulum (ER) function, and nitric oxide synthase (NOS).24

Obesity and Inflammatory Stress: Adipokines

Chronic nutrient overload leads to an energy imbalance, which manifests as an increase in the size of adipose depots with both greater adipocyte size (hypertrophy) and an increase in adipocyte number (hyperplasia). This adipogenesis implies the differentiation of preadipocytes into mature and secreting adipocytes,42 which release a large number of cytokines. Collectively, these bioactive peptides and proteins are termed “adipokines” and act as potent paracrine or endocrine molecules.43 Their

Biomarkers of Oxidative Stress

Oxidative stress is a multifaceted process and is difficult to quantify. Because of the increasing scientific interest on this subject in nutrition research, it is important to assess the oxidant status of an individual under pathologic nutritional conditions in several contexts, including (1) monitoring disease development, (2) following any form of intervention, and (3) monitoring treatment response. A set of noninvasive measurements of oxidative stress has been developed (Table I).56

Studies in Children and Adolescents

Evidence of obesity-induced oxidative stress in adults has emerged in the past several years,95 and more recently in children. Most studies have been cross-sectional in nature and have compared obese vs normal children (Table II). In the first studies of obesity and oxidative stress in children, researchers found an increase in individual parameters that indicated an increase in the oxidative response. Erdeve et al96 reported that the enzyme Cu/Zn-SOD was significantly higher in obese children

Interconnection of Oxidative and Inflammatory Stress in Obesity

Clinical studies of obese subjects have observed an association between the plasma levels of adipokines and markers of inflammation and/or oxidative stress.130 Little information, however, is available from studies in children (Table V). The levels of the proinflammatory adipokine, leptin, were correlated strongly with MDA levels in prepubertal children,131 who also showed an increase in homocysteine. Yilmaz et al132 also observed a positive correlation between BMI and MDA levels, to

Obesity, Oxidative Stress, Inflammation, and Endothelial Dysfunction

Endothelial dysfunction is defined broadly as a failure of the endothelium to serve its normal physiologic and protective functions. In addition to providing a physical barrier between the vessel wall and lumen, endothelial cells produce vasoactive substances and secrete several mediators that regulate platelet aggregation, coagulation and fibrinolysis. The endothelium also modulates the proliferation and injury response of the vascular smooth muscle layer. Endothelial dysfunction is

Conclusion

Obesity is a well-established metabolic and cardiovascular risk factor. Recent advances have increased our understanding of the cellular mechanisms, whereby adiposity induces adverse local and systemic effects. These mechanisms include adipocyte intracellular lipid accumulation, oxidative mitochondrial and ER stress with associated changes in circulating adipokines, and the actions of inflammatory mediators. These events can lead in turn to measurable increases in oxidative stress and may be

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