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

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 α-tocopherol and γ-tocopherol, major vitamin E isoforms, on the interaction between macrophages and adipocytes with regard to obesity-induced inflammation and insulin resistance.

Hypertrophied 3T3-L1 adipocytes were cocultured with RAW 264.7 macrophages and treated with α-tocopherol or γ-tocopherol at 12.5, 25, and 50 µM. The inflammatory cytokines (monocyte chemoattractant protein-1, tumor necrosis factor-α, and interleukin-6) and free fatty acid (FFA) release were measured by assay kits, and nuclear factor-kappaB (NF-κB) and c-Jun NH₂ terminal kinase (JNK) signals were evaluated by immunoblotting. Glucose uptake was measured with a fluorescent glucose derivative.

Treatment with α-tocopherol and γ-tocopherol restrained the coculture-induced increase in cytokines and FFA release. γ-Tocopherol exhibited greater suppression of inflammatory cytokines at 12.5 and 25 µM (P < 0.001). Both tocopherols inhibited NF-κB activation by limiting translocation of NF-κB (p65) to the nucleus, with γ-tocopherol showing a stronger effect compared to α-tocopherol. α-Tocopherol inhibited JNK phosphorylation at 50 μM, whereas γ-tocopherol did not. Furthermore, coculture with macrophages impaired glucose uptake in response to insulin, but both tocopherols restored insulin responsiveness (P < 0.01).

α-Tocopherol and γ-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.