Am J Physiol Heart Circ Physiol. 2026 Nov 1;331(5):H1718-H1730. doi: 10.1152/ajpheart.90085.2026. Epub 2026 Oct 13.
ABSTRACT
Elevated plasma ceramides and microvascular endothelial dysfunction are separately implicated in the incidence of cardiovascular disease. Exogenous exposure and endogenous accumulation of ceramide causes microvascular endothelial dysfunction in isolated human microvessels ex vivo; however, the impact of increased plasma ceramide on in vivo human microvascular function is unknown. We measured peripheral microvascular endothelial function in young, healthy adults before and after increasing plasma ceramide levels via high-fat meal. We hypothesized that acute increases in plasma ceramide would induce peripheral microvascular dysfunction. Twenty-three healthy adults (12 males and 11 females) participated in this double-blind, randomized controlled, crossover trial. In vivo microvascular function and perfusion were assessed with laser Doppler flowmetry (LDF) using local heating and incident dark-field microscopy imaging, respectively. Plasma ceramides were quantified and microvascular function was assessed at baseline and 2 and 4 h post ingestion of a meal rich in long (LCT)- or medium (MCT)-chain fatty acids. Acute consumption of a LCT meal increased (P < 0.001) circulating ceramide concentrations in female participants only. Nitric oxide-dependent and maximal dilation, assessed via LDF, were similarly reduced after the intake of either a MCT or LCT meal, with no sex differences observed. No change in microvascular density and perfusion was observed after the consumption of either meal. Results suggest that an acute increase in plasma ceramide is not sufficient to further impair postprandial microvascular function, as both meals similarly reduced microvascular function despite ceramide elevations occurring only after the LCT meal. Future studies should investigate how repeated elevations in ceramide levels affect microvascular function.NEW & NOTEWORTHY Acute consumption of a long-chain fatty acid-rich meal increased circulating ceramides in a sex-specific manner, with elevations observed only in females. Despite this, in vivo microvascular endothelial function was similarly impaired after both medium- and long-chain fatty acid-rich meals, with no differences observed between sexes. Further studies are needed to define the role of ceramide-induced microvascular dysfunction and the long-term cardiovascular impact of repeated exposure.
PMID:42932507 | DOI:10.1152/ajpheart.90085.2026