Urinary prostaglandin D2 and E2 metabolites associate with abdominal obesity, glucose metabolism, and triglycerides in obese subjects

Sven-Christian Pawelzik (1) , Antoine Avignon (2, 3) , Helena Idborg (1) , Catherine Boegner (3) , Françoise Stanke-Labesque (4) , Per-Johan Jakobsson (1) , Ariane Sultan (2, 3) , Magnus Bäck (1, 5)

1 Karolinska Institutet [Stockholm]
2 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
3 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
4 HP2 - Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire
5 DCAC - Défaillance Cardiovasculaire Aiguë et Chronique

Obesity is associated with low-grade chronic inflammation, which contributes to the development of the metabolic syndrome and its associated complications, such as insulin resistance and type-2 diabetes. There is limited data from animal and human studies about the local generation of pro-inflammatory prostanoid lipid mediators in white adipose tissue. However, the link between systemic prostanoid levels and parameters characterizing the metabolic syndrome is missing in human obesity. Therefore, we performed a targeted lipidomic analysis using urine samples from obese human subjects (n = 45) and show for the first time in humans that systemic urinary prostanoid levels correlate with metabolic parameters that indicate a dysregulated glucose and triglyceride metabolism. We identified tetranor-PGDM and tetranor-PGEM as the two major urinary prostanoid metabolites in these subjects with levels of 247 ± 31 and 23.3 ± 4.0 pmol/mg creatinine, respectively. Tetranor-PGDM was significantly associated with serum triglycerides, while tetranor-PGEM was associated with abdominal obesity as defined by an increased waist-to-hip ratio (WHR), with glycated hemoglobin (HbA1c), and with impaired oral glucose tolerance. These results confirm the previously established notion of low-grade chronic inflammation in obesity and further identify an association of the prostanoid pathway with obesity-associated dyslipidemia, abdominal obesity, and insulin resistance.

Mots clés: inflammation; metabolic syndrome; cyclooxygenase (COX); tetranor-PGDM; tetranor-PGEM; obesity

Domaines: Endocrinologie et métabolisme

Sven-Christian Pawelzik, Antoine Avignon, Helena Idborg, Catherine Boegner, Françoise Stanke-Labesque, et al.. Urinary prostaglandin D2 and E2 metabolites associate with abdominal obesity, glucose metabolism, and triglycerides in obese subjects. Prostaglandins and Other Lipid Mediators, 2019, 145, pp.106361. ⟨10.1016/j.prostaglandins.2019.106361⟩. ⟨hal-02267011⟩