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. 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). 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 obesity. Altogether, these findings may impact the understanding and implementation of PPARα or GLP-1R agonists in the clinic.

中文翻译：

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PPARα 和 PPARβ/δ 与肥胖儿童白细胞中的促炎标志物呈负相关

肥胖形成的病理生理学特征容易导致代谢和心血管疾病的发展，严重影响公众健康。由儿童肥胖引发的免疫代谢成分的慢性失调是该疾病的一个常见但鲜为人知的方面。过氧化物酶体增殖物激活受体（PPAR）是一组对于不同组织的能量和免疫稳态至关重要的转录因子。此外，胰高血糖素样肽-1 受体 (GLP-1R) 激活不仅影响胰岛素分泌，而且还调节可能通过 PPAR 同种型介导的细胞因子谱。然而，PPAR 和 GLP-1R 在肥胖儿科患者白细胞中的作用仍不清楚。因此，我们检查了肥胖儿科人群白细胞中 PPAR 同种型和 GLP-1R 的表达及其与代谢、激素、炎症和人体测量标志物的相关性。与对照组相比，肥胖儿童和青少年的人体测量和身体成分参数、TG、VLDL、TG/HDL、机器人脂肪（%）/女性脂肪（%）（A/G%）指数和 HOMA 评分显着增加团体。肥胖参与者表现出促炎特征，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) 和 adipsin (p = 0.0397)，而脂联素则显示减少 (p = 0.0452)。肥胖受试者的白细胞中 PPARα 和 GLP-1R 的表达低于瘦受试者的白细胞。此外，PPARα 与 TNF-α 呈负相关（p = 0.0383），而 GLP-1R 未显示与任何炎症变量相关。然而，这两种受体都与腹部皮褶呈负相关。尽管组间 PPARβ/δ 表达相似，但它与 IL-8 水平呈负相关 (p = 0.0085)。PPARα 和 PPARβ/δ 表达分别与促炎标志物 TNF-α 和 IL-8 呈负相关，表明参与炎症调节，而在儿童肥胖中观察到炎症调节发生了改变。此外，肥胖参与者的白细胞中 PPARα 和 GLP-1R 下调。两种受体的低表达与腹部皮褶的增加相关，这表明脂肪分布中的作用可能间接影响不同免疫和脂肪细胞的细胞因子分泌，可能会因肥胖而引发炎症。总而言之，这些发现可能会影响 PPARα 或 GLP-1R 激动剂在临床上的理解和实施。