Abstract
Recent studies show that brown rice improves glucose intolerance and potentially the risk of diabetes, although the underlying molecular mechanisms remain unclear. One of the phytochemicals found in high concentration in brown rice is γ-oryzanol (Orz), a group of ferulic acid esters of phytosterols and triterpene alcohols. Here, we found that Orz stimulated differentiation of 3T3-L1 preadipocytes and increased the protein expression of adipogenic marker genes such as peroxisome proliferator-activated receptor gamma (PPAR-γ) and CCAAT/enhanced binding protein alpha (C/EBPα). Moreover, Orz significantly increased the glucose uptake in insulin-resistant cells and translocation of glucose transporter type 4 (GLUT4) from the cytosol to the cell surface. To investigate the mechanism by which Orz stimulated cell differentiation, we examined its effects on cellular signaling of the mammalian target of rapamycin complex 1 (mTORC1), a central mediator of cellular growth and proliferation. The Orz treatment increased mTORC1 kinase activity based on phosphorylation of 70-kDa ribosomal S6 kinase 1 (S6K1). The effect of Orz on adipocyte differentiation was dependent on mTORC1 activity because rapamycin blocks cell differentiation in Orz-treated cells. Collectively, our results indicate that Orz stimulates adipocyte differentiation, enhances glucose uptake, and may be associated with cellular signaling mediated by PPAR-γ and mTORC1.
Highlights
Insulin is an important anabolic hormone that promotes cell differentiation of 3T3-L1 preadipocytes by activating adipocyte-specific transcription factors including peroxisome proliferator-activated receptor-γ (PPAR-γ) and CCAAT/enhancer-binding protein α (C/EBPα) [1]
We investigated whether Orz regulates cell differentiation of 3T3-L1 preadipocytes via upregulation of adipogenic markers including PPAR-γ
Eight days following the initiation of differentiation, the cells were stained with Oil Red O, which demonstrated that Orz increased lipid accumulation (Figure 1A)
Summary
Insulin is an important anabolic hormone that promotes cell differentiation of 3T3-L1 preadipocytes by activating adipocyte-specific transcription factors including peroxisome proliferator-activated receptor-γ (PPAR-γ) and CCAAT/enhancer-binding protein α (C/EBPα) [1]. PPAR-γ has emerged as a potent insulin sensitizer and is used in the treatment of type 2 diabetes [2,3]. PPAR-γ is dramatically induced during adipogenesis and expressed predominantly in adipose tissue [4]. It is critical for the functions of mature adipocytes, including in lipid metabolism, adipokine secretion, and insulin sensitivity [5]. High-affinity ligands of PPAR-γ induce insulin-sensitizing factors such as adiponectin [6]. Rosiglitazone is one of the most potent PPAR-γ agonists in adipose tissues, which has prolonged anti-diabetic effects but causes serious side effects. Natural products, which have proven to be a promising resource for drug discovery, are believed to have minimal side effects
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