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

Abstract

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. Limited data from animal and human studies support 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 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 obese 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.