PPARα and PPARβ/δ are negatively correlated with proinflammatory markers in leukocytes of 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 pediatric obesity is a common but scarcely understo...
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| Format: | Article |
| Language: | English |
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BMC
2020-10-01
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| Series: | Journal of Inflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12950-020-00264-2 |
| _version_ | 1819212316982378496 |
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| author | Karina Vargas-Sánchez Laura Vargas Yenny Urrutia Iván Beltrán Ana Beatriz Rossi Hernán Yupanqui Lozano Jorge Guarín Monica Losada-Barragán |
| author_facet | Karina Vargas-Sánchez Laura Vargas Yenny Urrutia Iván Beltrán Ana Beatriz Rossi Hernán Yupanqui Lozano Jorge Guarín Monica Losada-Barragán |
| author_sort | Karina Vargas-Sánchez |
| collection | DOAJ |
| description | 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 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 obesity. Altogether, these findings may impact the understanding and implementation of PPARα or GLP-1R agonists in the clinic. |
| first_indexed | 2024-12-23T06:41:02Z |
| format | Article |
| id | doaj.art-7ffb8447ddd840c0908a5b08ab5cce31 |
| institution | Directory Open Access Journal |
| issn | 1476-9255 |
| language | English |
| last_indexed | 2024-12-23T06:41:02Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Inflammation |
| spelling | doaj.art-7ffb8447ddd840c0908a5b08ab5cce312022-12-21T17:56:42ZengBMCJournal of Inflammation1476-92552020-10-0117111310.1186/s12950-020-00264-2PPARα and PPARβ/δ are negatively correlated with proinflammatory markers in leukocytes of an obese pediatric populationKarina Vargas-Sánchez0Laura Vargas1Yenny Urrutia2Iván Beltrán3Ana Beatriz Rossi4Hernán Yupanqui Lozano5Jorge Guarín6Monica Losada-Barragán7Research group of Translational Neurosciences, School of Medicine, Universidad de los AndesBiología celular y funcional e ingeniería de biomoléculas, Universidad Antonio NariñoBiología celular y funcional e ingeniería de biomoléculas, Universidad Antonio NariñoBiología celular y funcional e ingeniería de biomoléculas, Universidad Antonio NariñoGRINCIBIO. Universidad Antonio NariñoDEXA DIABGRINCIBIO. Universidad Antonio NariñoBiología celular y funcional e ingeniería de biomoléculas, Universidad Antonio NariñoAbstract 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 obesity. Altogether, these findings may impact the understanding and implementation of PPARα or GLP-1R agonists in the clinic.http://link.springer.com/article/10.1186/s12950-020-00264-2ObesityChildrenAdolescentsPPARGLP-1RCytokines |
| spellingShingle | Karina Vargas-Sánchez Laura Vargas Yenny Urrutia Iván Beltrán Ana Beatriz Rossi Hernán Yupanqui Lozano Jorge Guarín Monica Losada-Barragán PPARα and PPARβ/δ are negatively correlated with proinflammatory markers in leukocytes of an obese pediatric population Journal of Inflammation Obesity Children Adolescents PPAR GLP-1R Cytokines |
| title | PPARα and PPARβ/δ are negatively correlated with proinflammatory markers in leukocytes of an obese pediatric population |
| title_full | PPARα and PPARβ/δ are negatively correlated with proinflammatory markers in leukocytes of an obese pediatric population |
| title_fullStr | PPARα and PPARβ/δ are negatively correlated with proinflammatory markers in leukocytes of an obese pediatric population |
| title_full_unstemmed | PPARα and PPARβ/δ are negatively correlated with proinflammatory markers in leukocytes of an obese pediatric population |
| title_short | PPARα and PPARβ/δ are negatively correlated with proinflammatory markers in leukocytes of an obese pediatric population |
| title_sort | pparα and pparβ δ are negatively correlated with proinflammatory markers in leukocytes of an obese pediatric population |
| topic | Obesity Children Adolescents PPAR GLP-1R Cytokines |
| url | http://link.springer.com/article/10.1186/s12950-020-00264-2 |
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