Single high-fat challenge and trained innate immunity: A randomized controlled cross-over trial

Area of Science:

• Immunology
• Metabolic Health
• Cardiovascular Disease Research

Background:

• Trained immunity is a persistent pro-inflammatory monocyte phenotype triggered by stimuli like oxidized lipoproteins.
• In mice, high-fat diets induce trained immunity, worsening atherosclerosis.
• The effect of a single high-fat challenge on trained immunity in humans remains unclear.

Purpose of the Study:

• To investigate if a single high-fat challenge induces trained immunity in humans.
• To explore the in vitro and in vivo effects of high-fat meals on monocyte phenotype.

Main Methods:

• A randomized controlled cross-over study involving 14 healthy individuals.
• Administration of high-fat or reference shakes, with blood sampling at multiple time points.
• In vitro incubation of monocytes with post-shake serum and in vivo assessment of monocyte function.

Main Results:

• Serum from individuals after a high-fat shake induced trained immunity in donor monocytes in vitro, regulated by Toll-like receptor 4.
• This in vitro effect was independent of triglyceride-rich lipoproteins and metabolic endotoxemia.
• No significant changes in monocyte phenotype or function were observed in vivo following the high-fat challenge.

Conclusions:

• A high-fat challenge alters serum composition, with the potential to induce trained immunity in vitro.
• This in vitro potential for trained immunity does not translate to a persistent hyperinflammatory monocyte phenotype in vivo in humans.
• Further research is needed to understand the long-term implications of dietary fat on immune responses.