Relationship Between Hormonal Milieu and Oxidative Stress in Childhood Obesity: A Physiopathological Basis for Antioxidant Treatment and Prevention of Cardiovascular Risk
Pp. 149-203 (55)
Antonio Mancini, Francesco Leo, Chantal Di Segni, Sebastiano Raimondo and Aurora Natalia Rossodivita
The thrifty genotype, exposed to modern and industrialized societies,
characterized by food availability and reduced physical activity, recently culminated in
an epidemic obesity of giant proportions. Even more alarming than the figures
regarding adult obesity is the increasing rate of obese children that has augmented
almost 3-fold within the last 3 decades.
Obesity is associated with significant adverse effects on health, including metabolic,
endocrine, cardiovascular, gastrointestinal, respiratory, neurologic, psychiatric,
hematologic, and skeletal complications, and development of some types of
malignancies. Studies strongly suggest that vascular, histopathological and metabolic
changes begin in childhood. The development of metabolic problems associated with
obesity during childhood track into adulthood increases the risk for type 2 diabetes,
dyslipidemia and early cardiovascular disease.
In this paper, firstly we examine the numerous links between neuroendocrine peptides
and cytokines, which contribute to inflammation and oxidative stress (OS) in obesity.
A number of cytokine, mediators of inflammation, are produced by adipose tissue. In
obese patients, increase in IL-6, C reactive protein (CRP), TNF-alpha and decrease in
adiponectin and IL-10, induce pro-inflammatory stage, resulting in insulin resistance
and endothelial dysfunction. Decreasing the levels of chronic inflammation and OS in
childhood may prevent subsequent metabolic derangement along with increased
cardiovascular morbidity and mortality in adulthood. OS has been proposed to be a
potential mechanism linking obesity and endothelial dysfunction. In fact, oxidative
reactions are critical in all the events which lead to atherogenesis. OS plays an
important role in the pathogenesis of vascular alterations by either triggering
exacerbating the biochemical processes accompanying endothelial dysfunction.
The production of Radical Oxygen species (ROS) and Radical Nitrogen Species (RNS)
can occur at the cellular level in response to metabolic overload caused by an
overabundance of macronutrients. Excessive generation of ROS in adipose tissue
occurs by several interrelated pathophysiologic mechanisms, including nutrient
metabolic overload, mitochondrial dysfunction, and endothelial reticulum stress. ROS
generation is maintained by an inflammatory response, sustaining a vicious cycle.
Puberty alters some of the inflammatory markers associated with endothelial
dysfunction (adipocytokine levels, OS and insulin sensitivity) in obese children.
However, other than to inflammation, OS can be related to hormonal derangement in a
reciprocal way. Some hormones influence antioxidant levels, but OS also can modify
synthesis, activity and metabolism of hormones. Therefore, in the second section we
examine some hormonal patterns which are influenced by obesity and their role in the
regulation of antioxidant systems. In conclusion it seems that oxidative stress is
certainly related to systemic inflammation but also to hormonal derangement.
Aside from the excess energy intake, nutrients have a specific role in the development
of inflammation via the regulation of adipokine gene expression and secretion. In this
way, it is possible to choose “non-inflammatory” or “anti-inflammatory” foods to
minimize postprandial OS and inflammation. Therefore, lifestyle modifications,
consisting in a reduction of caloric intake, a diet focused on particular macronutrient or
micronutrient intake, and the encouragement of a regular exercise program with a
personalized format, type and duration may reduce the consequences of childhood
obesity. In particular we review the role of natural antioxidant in diet, as well as the
administration of pharmacological antioxidants. Whether this approach is effective in
improving vascular function in the short-term, but also in adult life remains to be
Antioxidants, Childhood, Metabolic syndrome, Obesity, Oxidative
Departments of Medical Sciences and Pediatrics, Catholic University of the Sacred Heart, Rome, Italy.