Review ArticleOxidant mechanisms in childhood obesity: the link between inflammation and oxidative stress
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
References (145)
- et al.
High adiposity and high body mass index-for-age in US children and adolescents overall and by race-ethnic group
Am J Clin Nutr
(2010) - et al.
General and abdominal obesity and abdominal visceral fat accumulation associated with coronary artery calcification in Korean men
Atherosclerosis
(2010) Oxidative stress: a dead end or a laboratory hypothesis?
Biochem Biophys Res Commun
(2007)- et al.
Free radicals and antioxidants in normal physiological functions and human disease
Int J Biochem Cell Biol
(2007) - et al.
Toxicological and pathophysiological roles of reactive oxygen and nitrogen species
Toxicology
(2010) - et al.
Enhanced concentrations of relevant markers of nitric oxide formation after exercise training in patients with metabolic syndrome
Nitric Oxide
(2008) - et al.
The role of antioxidants and antioxidant-related enzymes in protective responses to environmentally induced oxidative stress
Mutat Res
(2009) - et al.
Both lipid and protein intakes stimulate increased generation of reactive oxygen species by polymorphonuclear leukocytes and mononuclear cells
Am J Clin Nutr
(2002) - et al.
Mitochondrial dysfunction is induced by high levels of glucose and free fatty acids in 3T3-L1 adipocytes
Mol Cell Endocrinol
(2010) - et al.
Subcutaneous fat in normal and diseased states 3. Adipogenesis: from stem cell to fat cell
J Am Acad Dermatol
(2007)