title: Tocotrienol suppresses adipocyte differentiation and Akt phosphorylation in 3T3-L1 preadipocytes.
abstract: In vivo studies show that alpha-tocotrienol and gamma-tocotrienol accumulate in adipose tissue. Furthermore, a recent study reports that the oral administration of gamma-tocotrienol from a tocotrienol-rich fraction from palm oil (TRF) decreases body fat levels in rats. The objective of this study was to evaluate the effect of TRF and its components on adipocyte differentiation in 3T3-L1 preadipocytes, which differentiated into adipocytes in the presence of 1.8 micromol/L insulin. TRF suppressed the insulin-induced mRNA expression of adipocyte-specific genes such as PPARgamma, adipocyte fatty acid-binding protein (aP2), and CCAAT/enhancer-binding protein-alpha (C/EBPalpha) compared with the differentiation of 3T3-L1 preadipocytes into adipocytes only in the presence of insulin. To confirm the suppressive effect of TRF, the major components of TRF, such as alpha-tocotrienol, gamma-tocotrienol, and alpha-tocopherol, were investigated. Alpha-tocotrienol and gamma-tocotrienol decreased the insulin-induced PPARgamma mRNA expression by 55 and 90%, respectively, compared with insulin, whereas alpha-tocopherol increased the mRNA expression. In addition, gamma-tocotrienol suppressed the insulin-induced aP2 and C/EBPalpha mRNA expression, triglyceride accumulation, and PPARgamma protein levels compared with insulin. The current results also revealed that gamma-tocotrienol inhibited the insulin-stimulated phosphorylation of Akt but not extracellular signal-regulated kinase (ERK)1/2 in the insulin signaling pathway of 3T3-L1 preadipocytes. Thus, the antiadipogenic effect of TRF depends on alpha-tocotrienol and gamma-tocotrienol, and gamma-tocotrienol may be a more potent inhibitor of adipogenesis than alpha-tocotrienol. Therefore, the results of this study suggest that tocotrienol suppresses insulin-induced differentiation and Akt phosphorylation in 3T3-L1 preadipocytes. Furthermore, tocotrienol could act as an antiadipogenic vitamin in the nutrient-mediated regulation of body fat through its effects on differentiation.
authors.affiliation: Internal Medicine 1, National Defense Medical College, Tokorozawa-shi, Saitama 359-8513, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Uto-Kondo
authors.forename: Reiko
authors.initials: R
authors.lastname: Ohmori
authors.forename: Chikako
authors.initials: C
authors.lastname: Kiyose
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Kishimoto
authors.forename: Hisako
authors.initials: H
authors.lastname: Saito
authors.forename: Osamu
authors.initials: O
authors.lastname: Igarashi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kondo
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D051379:Mice; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D000073878:Palm Oil; D010766:Phosphorylation; D010938:Plant Oils / Q000737:chemistry; D024508:Tocotrienols / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D010938:Plant Oils; D024508:Tocotrienols; D000073878:Palm Oil; D051058:Oncogene Protein v-akt