PPARα and PPARβ/δ Expression is Associated with Proinflammatory Markers in an Obese Pediatric Population

Abstract

Background Obesity configures a pathophysiological profile that predisposes the development of metabolic and cardiovascular diseases, critically impacting public health. The chronic dysregulation of immuno-metabolic components triggered by obesity directly affects the metabolism of various tissues. Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors and transcription factors essential for energy homeostasis of different tissues. Despite its wide-ranging expression and function, the functional mismatch of the PPAR subtypes establish biological mechanisms responsible for metabolic diseases from childhood. In addition, the glucagon-like peptide-1 receptor (GLP-1R) activation can influence insulin secretion, but also the cytokine profile possibly mediated through PPARγ activation. However, to date, the role of PPARs and GLP-1R in leukocytes from obese pediatric patients has been unclear. Therefore, we examined the expression of PPARs isotypes and GLP-1R, and its correlation with metabolic, hormonal, inflammatory, and anthropometric markers in an obese pediatric population. Results Obese children and adolescents presented a significant increase in anthropometric and body composition parameters, TG, VLDL, TG/HDL, A/G index, and HOMA score when compared to the control group. Obese participants exhibited a pro-inflammatory profile with an augment of IL-8 (p = 0,0081), IL-6 (p = 0,0005), TNF-α (p = 0,0004), IFN-γ (p = 0,0110), MCP-1 (p = 0,0452), and adipsin (p = 0,0397), whereas displayed a reduction of adiponectin (p = 0,0452). The expression of PPARα and GLP-1R was lower in the leukocytes from obese participants than in lean subjects. Furthermore, PPARα correlates negatively with TNF-α (p = 0,0383), while GLP-1R did not show correlation with any inflammatory variable. However, both receptors correlate negatively with the abdominal skinfold. Although PPARβ/δ expression was similar between groups, it was negatively associated with IL-8 levels (p = 0,0085). Conclusions PPARα and PPARβ/δ expression are negatively associated with the proinflammatory markers TNF-α and IL-8, respectively, suggesting participation in the regulation of inflammation observed in pediatric obesity. Furthermore, PPARα and GLP-1R are downregulated in leukocytes from obese children and adolescents, and both receptors are associated with the abdominal skinfold suggesting a role in fat distribution that could indirectly affect the function of different immune cells and the secreted cytokines. Thereby, these findings may impact the understanding and implementation of PPARα or GLP-1R agonists in the clinic.