Peroxisome proliferator-activated receptor (PPAR) α and δ activators induce ICAM-1 expression in quiescent non stimulated endothelial cells

Naidenow, Julia; Hrgović, Igor; Doll, Monika; Hailemariam-Jahn, Tsige; Lang, Victoria; Kleemann, Johannes; Kippenberger, Stefan; Kaufmann, Roland; Zöller, Nadja; Meißner, Markus

doi:10.1186/s12950-016-0135-2

Cited by 13 publications

(7 citation statements)

References 48 publications

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“…Although the direct link of PPARβ/δ to IL-8 is suggestive, some studies have already related the activation of PPARβ/δ with the modulation of expression of IL-8 in endothelial cells and endometrium tissue participating in in ammation [33][34][35]. In line with this evidence, our results suggest that a decrease in the PPARβ/δ expression in leukocytes might consequently augment the IL-8 levels and, thereby, the in ammatory response during obesity.…”

Section: Discussionsupporting

confidence: 84%

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

Vargas-Sánchez¹,

Vargas²,

Urrutia³

et al. 2020

Preprint

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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.

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Section: Discussionsupporting

confidence: 84%

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

Vargas-Sánchez¹,

Vargas²,

Urrutia³

et al. 2020

Preprint

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show abstract

“…The PPARα is a ligand-activated transcription factor belonging to the superfamily of nuclear hormone receptors. By modulating gene expression, it plays key roles in maintaining glucose and lipid homeostasis and inhibiting inflammation (71). The PPARα activation has also been shown to induce rapid, cellular changes without requiring transcription (72).…”

Section: Discussionmentioning

confidence: 99%

Cellular Distribution of Canonical and Putative Cannabinoid Receptors in Canine Cervical Dorsal Root Ganglia

et al. 2019

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Growing evidence indicates cannabinoid receptors as potential therapeutic targets for chronic pain. Consequently, there is an increasing interest in developing cannabinoid receptor agonists for treating human and veterinary pain. To better understand the actions of a drug, it is of paramount importance to know the cellular distribution of its specific receptor(s). The distribution of canonical and putative cannabinoid receptors in the peripheral and central nervous system of dogs is still in its infancy. In order to help fill this anatomical gap, the present ex vivo study has been designed to identify the cellular sites of cannabinoid and cannabinoid-related receptors in canine spinal ganglia. In particular, the cellular distribution of the cannabinoid receptors type 1 and 2 (CB1 and CB2) and putative cannabinoid receptors G protein-coupled receptor 55 (GPR55), nuclear peroxisome proliferator-activated receptor alpha (PPARα), and transient receptor potential vanilloid type 1 (TRPV1) have been immunohistochemically investigated in the C6–C8 cervical ganglia of dogs. About 50% of the neuronal population displayed weak to moderate CB1 receptor and TRPV1 immunoreactivity, while all of them were CB2-positive and nearly 40% also expressed GPR55 immunolabeling. Schwann cells, blood vessel smooth muscle cells, and pericyte-like cells all expressed CB2 receptor immunoreactivity, endothelial cell being also PPARα-positive. All the satellite glial cells (SGCs) displayed bright GPR55 receptor immunoreactivity. In half of the study dogs, SGCs were also PPARα-positive, and limited to older dogs displayed TRPV1 immunoreactivity. The present study may represent a morphological substrate to consider in order to develop therapeutic strategies against chronic pain.

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“…Although the direct link of PPARβ/δ to IL-8 is suggestive, some studies have already related the activation of PPARβ/δ with the modulation of expression of IL-8 in endothelial cells and in endometrium participating in inflammation [ 27 – 29 ]. In line with this evidence, our results suggest that a decrease in the PPARβ/δ expression in leukocytes might consequently augment IL-8 levels and, thereby, the inflammatory response during obesity.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

show abstract

Peroxisome proliferator-activated receptor (PPAR) α and δ activators induce ICAM-1 expression in quiescent non stimulated endothelial cells

Cited by 13 publications

References 48 publications

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

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

Cellular Distribution of Canonical and Putative Cannabinoid Receptors in Canine Cervical Dorsal Root Ganglia

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

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