Multi-omics analysis identifies potential mechanisms by which high glucose accelerates macrophage foaming

Area of Science:

• Biochemistry
• Cell Biology
• Metabolomics

Background:

• Diabetic patients exhibit higher atherosclerotic morbidity.
• Hyperglycemia accelerates foam cell formation, a key process in atherosclerosis.
• The precise molecular mechanisms of high glucose-induced foam cell formation are not fully understood.

Purpose of the Study:

• To elucidate the molecular mechanisms by which high glucose promotes foam cell formation in macrophages.
• To investigate the impact of high glucose on lipid accumulation, efflux, and inflammation in macrophages.
• To identify metabolic and transcriptional alterations in macrophages under high glucose conditions.

Main Methods:

• THP-1-derived macrophages were differentiated into M1 macrophages and activated with ox-LDL under high glucose or normal conditions.
• Lipid accumulation was assessed using Oil red O staining and total cholesterol detection.
• Gene expression analysis (qRT-PCR), metabolomics, and transcriptomics were employed to investigate molecular changes.

Main Results:

• High glucose significantly increased lipid accumulation (droplets and cholesterol) and inflammation (IL1B, TNF) while decreasing lipid efflux (ABCG1).
• Multi-omics analysis revealed alterations in 392 metabolites and 293 genes, primarily affecting glycerolipid, glycerophospholipid, and arachidonic acid metabolism.
• High glucose suppressed triglyceride hydrolase (LIPG, LPL) transcription, leading to triglyceride deposition and foam cell formation, and accumulated pro-atherosclerotic lipids.

Conclusions:

• High glucose promotes foam cell formation by disrupting macrophage lipid metabolism and inflammatory responses.
• The study identified specific metabolic pathways (glycerolipid, glycerophospholipid, arachidonic acid) disrupted by high glucose.
• This research provides novel insights into the mechanisms of glucose-induced foam cell formation using a multi-omics approach.