PPARα and PPARβ/δ are negatively correlated with proinflammatory markers in leukocytes of an obese pediatric population

• Published in: Journal of inflammation (London, England) England), 2020-10, Vol.17 (1), p.1-35, Article 35
• Main Authors: Vargas-Sánchez, Karina, Vargas, Laura, Urrutia, Yenny, Beltrán, Iván, Rossi, Ana Beatriz, Lozano, Hernán Yupanqui, Guarín, Jorge, Losada-Barragán, Monica
• Format: Article
• Language: English
• Subjects: Adiponectin; Adolescents; Body composition; Body fat; Cardiovascular disease; Cardiovascular diseases; Children; Cytokines; Gene expression; GLP-1R; Glucagon; Glucagon-like peptide 1; Glucose; Health care; High density lipoprotein; Homeostasis; Inflammation; Insulin; Insulin secretion; Interleukin 6; Interleukin 8; Isotypes; Leukocytes; Lipoproteins (very low density); Metabolism; Monocyte chemoattractant protein 1; Obesity; Pediatrics; Peroxisome proliferator-activated receptors; PPAR; Public health; Teenagers; Transcription factors; Tumor necrosis factor-α; γ-Interferon
• ISSN: 1476-9255; 1476-9255
• DOI: 10.1186/s12950-020-00264-2

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 pediatric obesity is a common but scarcely understood aspect of the disease. Peroxisome proliferator-activated receptors (PPARs) are a group of transcription factors essential for energy and immune homeostasis of different tissues. Besides, the glucagon-like peptide-1 receptor (GLP-1R) activation influences insulin secretion, but also regulates the cytokine profile possibly mediated through a PPAR isotype. However, the role of PPARs and GLP-1R in leukocytes from obese pediatric patients remains unclear. Therefore, we examined the expression of PPARs isotypes and GLP-1R in leukocytes, 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, android fat (%)/gynoid fat (%) (A/G%) index, and HOMA score when compared with 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 correlated with the proinflammatory markers TNF-α and IL-8, respectively, suggesting participation in the regulation of inflammation which was observed to be altered in pediatric obesity. Furthermore, PPARα and GLP-1R are downregulated in leukocytes from obese participants. The low expression of both receptors is correlated with an increase in abdominal skinfold, suggesting a role in fat distribution that could indirectly affect cytokine secretion from different immune and adipose cells, likely triggering an inflammatory profile as a consequence of obes