Inverse association between circulating hexosylceramides and cardiometabolic risk factors in adult women with overweight-obesity

Altered sphingolipid profiles are associated with obesity and increased cardiometabolic risk, and each lipid class has its own specificity. We hypothesize that overweight-obesity (OW-OB) is associated with an imbalance in the ceramides and hexosylceramides profile of adult women, which may be associated with alterations in the lipid profile (high-density lipoprotein cholesterol [HDLc], low-density lipoprotein cholesterol [LDLc], and total cholesterol). This study investigated the association between plasmatic sphingolipids, particularly ceramides and hexosylceramides, and cardiometabolic risk factors in adult women with OW-OB. Anthropometric measures, food consumption, biochemical measurements, and cardiometabolic parameters were obtained from 37 adult women with normal weight (n = 12) or OW-OB (n = 25). Flow injection analysis coupled with mass spectrometry-targeted metabolomics was used to determine the plasma concentrations of sphingolipids. Unsupervised clustering analysis of altered metabolites in women segregated normal weight and OW-OB classes into 2 distinct groups, revealing an overall association between altered metabolites and OW-OB. The OW-OB was associated with significantly decreased concentrations of multiple hexosylceramides and certain ceramide molecular species. The concentrations of hexosylceramides and ceramides were correlated with cardiometabolic risk factors, including total cholesterol, LDLc, HDLc, and triglyceride. Low plasma hexosylceramide is associated with OW-OB, high total cholesterol, and low HDLc in women. On the other hand, the bulk of ceramides was associated with elevated triglycerides and LDLc. Our data suggest that decreased hexosylceramide concentrations may be associated with cardiometabolic diseases in adult women with OW-OB.