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Published on: May 4, 2021
Tocotrienol suppresses adipocyte differentiation and Akt phosphorylation in 3T3-L1 preadipocytes
Harumi Uto-Kondo1, Reiko Ohmori, Chikako Kiyose
1Internal Medicine 1, National Defense Medical College, Tokorozawa-shi, Saitama 359-8513, Japan.
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.
Insights
Tocotrienols, found in palm oil, inhibit fat cell differentiation. Gamma-tocotrienol is a potent antiadipogenic compound, suppressing key gene and protein markers and affecting insulin signaling pathways.
Area of Science:
- Biochemistry
- Cell Biology
- Nutritional Science
Background:
- Tocotrienols, including alpha-tocotrienol and gamma-tocotrienol, accumulate in adipose tissue.
- Gamma-tocotrienol from palm oil's tocotrienol-rich fraction (TRF) has shown potential in reducing body fat in vivo.
- Adipocyte differentiation is a key process in fat tissue development and regulation.
Purpose of the Study:
- To investigate the effects of TRF and its components on adipocyte differentiation in 3T3-L1 preadipocytes.
- To determine if alpha-tocotrienol and gamma-tocotrienol suppress key markers of adipogenesis.
- To elucidate the specific molecular mechanisms, including insulin signaling pathways, involved in tocotrienol's antiadipogenic effects.
Main Methods:
- Utilized 3T3-L1 preadipocytes differentiated with insulin.
- Quantified mRNA expression of adipocyte-specific genes (PPARγ, aP2, C/EBPα) using RT-qPCR.
- Assessed triglyceride accumulation and protein levels of PPARγ.
- Investigated insulin signaling pathways by examining Akt and ERK1/2 phosphorylation.
Main Results:
- TRF significantly suppressed insulin-induced mRNA expression of PPARγ, aP2, and C/EBPα.
- Alpha-tocotrienol and gamma-tocotrienol decreased PPARγ mRNA expression, while alpha-tocopherol increased it.
- Gamma-tocotrienol demonstrated potent suppression of adipogenic gene and protein expression, triglyceride accumulation, and inhibited insulin-stimulated Akt phosphorylation.
Conclusions:
- Tocotrienols, particularly gamma-tocotrienol, exhibit significant antiadipogenic effects by inhibiting adipocyte differentiation in 3T3-L1 cells.
- The antiadipogenic action of TRF is attributed to its tocotrienol components, with gamma-tocotrienol being a more potent inhibitor.
- Tocotrienol's mechanism involves suppressing insulin-induced differentiation and Akt phosphorylation, suggesting a role as an antiadipogenic vitamin in body fat regulation.
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