d ‐δ‐Tocotrienol suppresses the differentiation of murine 3T3‐F442A preadipocytes (641.8)

Suppression of adipogenesis is one of the potential approaches in obesity prevention. The statins, competitive inhibitors of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG CoA) reductase, suppress the differentiation of adipocytes via mevalonate deprivation. We hypothesize that d ‐δ‐tocotrienol, a vitamin E molecule shown to accelerate the degradation of HMG CoA reductase, suppresses adipocyte differentiation and adipogenic gene expression. Adipo‐Red assay and oil Red O staining showed that an 8‐d incubation with 2.5 ‐ 10 μmol/L d ‐δ‐tocotrienol dose‐dependently reduced the intracellular triglyceride content of murine 3T3‐F442A adipocytes, reminiscent of the lovastatin (1.25 μmol/L) effect. Concomitantly, d ‐δ‐tocotrienol dose‐dependently inhibited glucose uptake by 3T3‐F442A cells and the expression of GluT4, pAKT, and HMG CoA reductase proteins. Rosiglitazone (1 µmol/L), an agonist of peroxisome proliferator activator receptor‐activated receptor γ ‐ a key mediator of adipocyte differentiation ‐ reversed the effects of d ‐δ‐tocotrienol on cellular lipid content and glucose uptake but not those of lovastatin. In contrast, mevalonate (100 µmol/L) reversed the effects of lovastatin. d ‐α‐Tocopherol at 10 µmol/L did not have any impact on 3T3‐F442A differentiation. Trypan blue staining showed no changes in cell viability following 48‐h incubation of 3T3‐F442A cells with d ‐δ‐tocotrienol (0‐80 µmol/L), suggesting that the adipogenesis‐suppressive activity of d ‐δ‐tocotrienol was independent of cytotoxicity. Dietary d ‐δ‐tocotrienol may have potential as anti‐adipogenesis compounds. Grant Funding Source : Supported by Texas Department of Agriculture and TWU Research Enhancement Program