Platelet Lipidome Fingerprint: New Assistance to Characterize Platelet Dysfunction in Obesity

Abstract

Obesity is associated with a pro-inflammatory and pro-thrombotic state that supports atherosclerosis progression and platelet hyper-reactivity. During the last decade, the platelet lipidome has been considered a treasure trove, as it is a source of biomarkers for preventing and treating different pathologies. The goal of the present study was to determine the lipid profile of platelets from non-diabetic, severely obese patients compared with their age- and sex-matched lean controls. Lipids from washed platelets were isolated and major phospholipids, sphingolipids and neutral lipids were analyzed either by gas chromatography or by liquid chromatography coupled to mass spectrometry. Despite a significant increase in obese patient’s plasma triglycerides, there were no significant differences in the levels of triglycerides in platelets among the two groups. In contrast, total platelet cholesterol was significantly decreased in the obese group. The profiling of phospholipids showed that phosphatidylcholine and phosphatidylethanolamine contents were significantly reduced in platelets from obese patients. On the other hand, no significant differences were found in the sphingomyelin and ceramide levels, although there was also a tendency for reduced levels in the obese group. The outline of the glycerophospholipid and sphingolipid molecular species (fatty-acyl profiles) was similar in the two groups. In summary, these lipidomics data indicate that platelets from obese patients have a unique lipid fingerprint that may guide further studies and provide mechanistic-driven perspectives related to the hyperactivate state of platelets in obesity.

Quantification of bulk lipid species in human platelets and their thrombin-induced release

“…Lipid species of basal platelets reported here were quite similar to the pattern described by Leidl et al 27 as well as by Valkonen et al 13 and align reasonably with those reported by Han et al 9 . Similar species profiles were also reported recently for platelets isolated from healthy subjects and obese patients 29 . However, we could not confirm the presence of short chain PC 18:0, 20:0, 24:0, which were found upregulated in platelets of acute www.nature.com/scientificreports/ coronary syndrome patients 30 .…”

Glycoursodeoxycholic Acid Alleviates Arterial Thrombosis via Suppressing Diacylglycerol Kinases Activity in Platelet

“…Previous studies have confirmed platelet hyperreactivity as a vital pathological factor contributing to high thrombotic risk in metabolic disorders such as obesity, diabetes, hypertension, and hyperlipidemia. 62–65 Notably, GUDCA, an endogenous bile acid species, exhibited significantly lower plasma levels in patients with hyperglycemia. 20 Our previous study, along with other publications, had also verified that GUDCA maintained metabolic homeostasis and ameliorated metabolic disorders including atherosclerosis, diabetes, and fatty liver disease.…”

Heterogeneity of platelets and their responses

“…Single-cell technologies have opened a unique window into understanding intraindividual heterogeneity among hematopoietic stem cells [ 17 ] and megakaryocytes [ 18 , 19 ]. Transcriptomics [ 20 ], proteomics [ 21 ], and novel lipidomics [ 22 ] have enabled multiple pathways to be examined simultaneously in large and varied cohorts of individuals.…”

“…Studies of the platelet proteome and phosphoproteome in obese individuals and matched controls have identified differentially activated signaling pathways that translate into altered in vitro aggregation phenotypes [ 80 , 81 ]. More recently, comprehensive study of platelet lipids—the “lipidome” —has revealed differences between obese and nonobese individuals [ 22 ].…”