Immunometabolic profiling of human monocytes in response to lipid exposure
Pubblicato online: 06 ago 2025
Pagine: 157 - 168
Ricevuto: 30 mag 2025
Accettato: 06 lug 2025
DOI: https://doi.org/10.2478/rrlm-2025-0021
Parole chiave
© 2025 Ion Bogdan Mănescu et al., published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.
Background
Monocytes are central in inflammation and atherogenesis. Postprandial lipemia is a known pro-atherogenic state, yet its impact on monocyte activation remains incompletely understood. This study aimed to investigate morphological and immunophenotypical changes in circulating monocytes following lipid exposure.
Methods
Monocytes from 19 healthy volunteers were analyzed at baseline (fasting/T0), three hours postprandially (T3), and after 24-hour incubation with autologous serum (T24). Flow cytometry was used to assess monocyte subsets (classical/CM, intermediate/IM, and nonclassical/NCM) based on CD14/CD16 expression, alongside markers of activation (CD11b, CD14), lipid uptake (BODIPY), and lipid handling (LDLR, CD36). Morphological parameters (FSC, SSC) were also evaluated.
Results
At T3, all monocyte subsets showed increased size, with CM and NCM also showing increased granularity (↑SSC). LDLR expression decreased in all subsets, while CD36 increased only in NCM. At T24, monocytes displayed further increase in size, as well as higher lipid accumulation and activation (CD11b, CD14, LDLR), particularly in CM and IM. NCMs uniquely increased in size while decreasing granularity and showed no rise in activation markers. Overall, IMs consistently exhibited the most proinflammatory phenotype, while NCMs retained an anti-inflammatory profile. A novel inverse correlation was found between BMI and monocyte LDLR expression.
Conclusions
These findings underscore the dynamic and subset-specific responses of monocytes to lipid exposure, highlighting intermediate monocytes as key proinflammatory players and suggesting a more quiescent role for non-classical monocytes. This phenotypic distinction may hold clinical relevance for early immune monitoring in cardiometabolic risk states, as well as for advancing novel therapeutic interventions targeting monocytes at the cellular level.