beta-Carotene accumulation in 3T3-L1 adipocytes inhibits the elevation of reactive oxygen species and the suppression of genes related to insulin sensitivity induced by tumor necrosis factor-alpha.

摘要

OBJECTIVE: beta-Carotene is an abundant carotenoid with potent antioxidative activities and accumulates in adipose tissue. However, its physiologic functions are poorly understood. In this study, we examined whether accumulation of beta-carotene for 4 d in insulin-resistant 3T3-L1 adipocytes alters the expression of genes related to insulin sensitivity. METHODS: The 3T3-L1 adipocytes were treated with/without 10 or 20 muM beta-carotene during differentiation for 4 d. The cells treated with 10 muM beta-carotene for 4 d were subsequently incubated with/without 5 ng/mL of tumor necrosis factor-alpha for 48 h in the medium without beta-carotene. The mRNA levels of genes in the cells and adiponectin protein levels in the medium were determined by real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Reactive oxygen species levels in the cells were assessed by oxidation of 2',7'-dichlorodihydrofluorescein diacetate. RESULT: beta-Carotene treatment at a concentration of 20 muM, but not 10 muM, in 3T3-L1 adipocytes during differentiation for 4 d enhanced the expression of genes related to insulin sensitivity, including adiponectin, adipocyte lipid-binding protein, glucose transporter-4, peroxisome proliferator-activated receptor-gamma2, and adiponectin protein in the medium. Tumor necrosis factor-alpha treatment repressed the expression of these genes and adiponectin protein in the medium and induced reactive oxygen species levels. In contrast, cells that accumulated beta-carotene at a concentration of 10 muM did not show these alterations. CONCLUSION: The accumulation of the beta-carotene in 3T3-L1 adipocytes restores the expression of genes related to insulin sensitivity and reactive oxygen species levels in insulin-resistant adipocytes.