Lhomme, M. | bioRxiv Science

bioRxiv2021

Lipidomic analysis of adipose-derived extracellular vesicles reveals their potential as lipid mediators of obesity-associated metabolic complications

Adipose extracellular vesicles (AdEV) transport lipids that could participate to the development of obesity-related metabolic dysfunctions. This study aimed to define mice AdEV lipid signature in either healthy or obesity context by a targeted LC-MS/MS approach. Distinct clustering of AdEV and visceral adipose tissue (VAT) lipidomes by principal component analysis reveals specific lipid composition of AdEV compared to source VAT. Comprehensive analysis identifies enrichment of ceramides and phosphatidylglycerols in AdEV compared to VAT in lean conditions. Lipid subspecies commonly enriched in AdEV highlight specific AdEV-lipid sorting. Obesity impacts AdEV lipidome, driving triacylglycerols and sphingomyelins enrichment in obese versus lean conditions. Obese mice AdEV also display elevated phosphatidylglycerols and acid arachidonic subspecies contents highlighting novel biomarkers and/or mediators of metabolic dysfunctions. Our study identifies specific lipid-fingerprints for plasma, VAT and AdEV that are informative of the metabolic status and underline the signaling capacity of lipids transported by AdEV in obesity-associated complications.

physiology↗

bioRxiv2020

HIGH FAT DIET STIMULATES BETA-OXIDATION, ALTERS ELECTRICAL PROPERTIES AND INDUCES ADIPOGENICITY OF ATRIA IN OBESE MICE

Metabolic disorders such as obesity are risk factors of atrial fibrillation, not only by sharing comorbidities but likely through their direct impact on atria, notably its adipogenicity. Here, we submitted mice that lack cardiac adipose tissue to a high fat diet and first studied the atrial metabolomic and lipidomic phenotypes using liquid chromatography-mass spectrometry. We found an increased consumption of free fatty acid by the beta-oxidation and an accumulation of long-chain lipids in atria of obese mice. Free fatty acid was the main substrate of mitochondrial respiration studied in the saponin-permeabilized atrial muscle. Conducted action potential recorded in atrial trabeculae was short, and ATP-sensitive potassium current was increased in perforated patch-clamp atrial myocytes of obese mice. There was histological and phenotypical evidence for an accumulation of adipose tissue in obese mice atria. Thus, an obesogenic diet transforms the energy metabolism, causes fat accumulation and induces electrical remodeling of atria myocardium. HIGHLIGHTS- Untargeted metabolomic and lipidomic analysis revealed that a high fat diet induces profound transformation of atrial energy metabolism with beta-oxidation activation and long-chain lipid accumulation. - Mitochondria respiration studied in atrial myocardial trabecula preferentially used Palmitoyl-CoA as energy substrate in obese mice. - Atria of obese mice become vulnerable to atrial fibrillation and show short action potential due to the activation of K-ATP dependent potassium current. - Adipocytes and fat molecular markers were detected in atria of obese mice together with an inflammatory profile consistence with a myocardial accumulation of fat.

physiology↗