Metabolic Adaptation of CD8⁺ T Cells Limits the Efficacy of Fatty Acid Oxidation Inhibition in Type 1 Diabetes - PubMed
3 days ago
- #Metabolic Adaptation
- #Type 1 Diabetes
- #CD8+ T cells
- Type 1 Diabetes Mellitus (T1D) is an autoimmune disease causing hyperglycemia due to immune-mediated destruction of pancreatic β-cells.
- Fatty acid oxidation (FAO) inhibitor trimetazidine (TMZ) was tested in non-obese diabetic mice (NOD) to delay T1D progression.
- TMZ enhanced mitochondrial membrane potential, suppressed FAO, and reduced activation and proliferation of human CD8+ T cells.
- In dysglycemic NOD mice, TMZ delayed T1D onset, lowered glycemia, and decreased islet CD4+/CD8+ T cell infiltration.
- Single-cell RNA sequencing showed depletion of FAO-high, stress-responsive cells and improved pancreatic health.
- Prolonged TMZ exposure led to compensatory upregulation of CPT1A in CD8+ T cells, counteracting early benefits.
- The study highlights metabolic adaptation as a key factor in autoimmune progression and validates FAO as a therapeutic target in T1D.