Avaliação e associação dos parâmetros metabólicos, inflamatórios e epigenéticos na obesidade infantil

Abstract

Obesity is defined as disproportional body weight for length with accumulation of adipose tissue. Dysregulation in the metabolic profile and the occurrence of low-grade inflammation are hallmarks of this condition. Inflammatory mechanisms, particularly, seem to be involved in the development of diseases that may appear with higher levels of adiposity. In children, obesity seems to follow the inflammatory pattern, although the literature about this theme is diffuse yet. In addition, it is necessary to consider that obesity has a multifactorial origin, with both genetic and environmental determinants. In this regard, it is important to give emphasis on epigenetic mechanisms, which contribute to the control of gene expression and can elicit a response to environmental changes. DNA methylation is one of such mechanisms. Generally speaking, it is important to promote transcription repression as it impedes the binding of transcription factors to gene promoters. The studies about DNA methylation on childhood obesity are incipient yet. In this sense, the objective of this study was to characterize childhood obesity under the perspective of metabolism, inflammation, and epigenetics through the evaluation of biochemical parameters, such as the lipidic profile and the level of hepatic enzymes; of the expression of the cytokines IL-8 and TGF-β and of the adipokines leptin and adiponectin; and of the DNA methylation in the genes of these inflammatory mediators. The biochemical parameters pointed out the occurrence of dyslipidemia and elevation of the levels of hepatic enzymes in the group of children with obesity, flow cytometry revealed higher expression of TGF-β and lower expression of IL-8 in childhood obesity, and ELISA showed elevation in the serum levels of leptin and decreased serum levels of adiponectin. DNA methylation analysis through methylation-specific PCR technique revealed reduced methylation levels in IL8 promoter in children with obesity. The levels of adipokines and the expression of cytokines were correlated. In the same way, methylation in IL8 promoter and the serum concentration of hepatic enzymes were also correlated. These data reinforce the picture showed by the literature of metabolic dysregulation, of changes in the expression of cytokines and adipokines, and of participation of DNA methylation in obesity. The alterations reported for IL-8 are surprising due to the literature depicting this cytokine as upregulated in inflammatory settings. However, it may be possible that its decreased levels in obesity might be an attempt to downregulate the inflammatory process.