α-Tocopherol and γ-tocopherol decrease inflammatory response and insulin resistance during the interaction of adipocytes and macrophages

BACKGROUND/OBJECTIVES: The infiltration of macrophages into adipose tissue mediates chronic inflammation that is associated with insulin resistance in obesity. Although vitamin E is beneficial against insulin resistance, its impact on adipose tissue inflammation has not been elucidated. This study aims to investigate the effects of alpha-tocopherol and gamma-tocopherol, major vitamin E isoforms, on the interaction between macrophages and adipocytes with regard to obesity-induced inflammation and insulin resistance. MATERIALS/METHODS: Hypertrophied 3T3-L1 adipocytes were cocultured with RAW 264.7 macrophages and treated with alpha-tocopherol or gamma-tocopherol at 12.5, 25, and 50 mu M. The and interleukin-6) and free fatty acid (FFA) release were measured by assay kits, and nuclear factor-kappaB (NF-kappa B) and c-Jun NH2 terminal kinase (JNK) signals were evaluated by immunoblotting. Glucose uptake was measured with a fluorescent glucose derivative. RESULTS: Treatment with alpha-tocopherol and gamma-tocopherol restrained the coculture-induced increase in cytokines and FFA release. gamma-Tocopherol exhibited greater suppression of inflammatory cytokines at 12.5 and 25 mu M (P < 0.001). Both tocopherols inhibited NF-kappa B activation by limiting translocation of NF-kappa B (p65) to the nucleus, with gamma-tocopherol showing a stronger effect compared to alpha-tocopherol. alpha-Tocopherol inhibited JNK phosphorylation at 50 mu M, whereas gamma-tocopherol did not. Furthermore, coculture with macrophages impaired glucose uptake in response to insulin, but both tocopherols restored insulin responsiveness (P < 0.01). CONCLUSION: alpha-Tocopherol and gamma-tocopherol effectively mitigate inflammation induced by adipocyte-macrophage interaction, thereby ameliorating coculture-induced insulin resistance. These findings suggest the therapeutic potential of tocopherols in managing obesity-related metabolic dysfunction.