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27-Hydroxycholesterol suppresses lipid accumulation by down-regulating lipogenic and adipogenic gene expression in 3T3-L1 cells

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Abstract

Cholesterol oxidation products (oxycholesterols) are produced from cholesterol by automatic and/or enzymatic oxidation of the steroidal backbone and side-chain. Oxycholesterols are present in plasma and serum, suggesting that oxycholesterols are related to the development and progression of various diseases. However, limited information is available about the absolute amounts of oxycholesterols in organs and tissues, and the physiological significance of oxycholesterols in the body. In the present study, we quantified the levels of 13 oxycholesterols in white adipose tissue (WAT) of mice and then evaluated correlations between each oxycholesterol level and WAT weight. The sum of the levels of 13 oxycholesterols in WAT (white adipose tissue) was 15.9 ± 3.4 μg/g of WAT weight and approximately 1 % of cholesterol level. Among oxycholesterols, the levels of 27-hydroxycholesterol (27-OH), an endogenous oxycholesterol produced by enzymatic oxidation, and the relative WAT weights were significantly negatively correlated. Next, we evaluated the effects of 27-OH on lipogenesis and adipogenesis in 3T3-L1 cells. TO901317 (TO), a potent and selective agonist for LXRα, significantly increased intracellular TAG contents, while 27-OH significantly reduced the contents to half when compared with control (DMSO) and completely abolished the effect of TO. In addition, 27-OH significantly reduced the mRNA levels of lipogenic (LXRα and FAS) and adipogenic genes (PPARγ and aP2) during adipocyte maturation of 3T3-L1 cells. In conclusion, our results indicate that 27-OH suppresses lipid accumulation by down-regulating lipogenic and adipogenic gene expression in 3T3-L1 cells.

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Acknowledgments

This work was supported by JSPS KAKENHI Grant Numbers 21580144, 23780138.

Authors’ contributions

B.S. wrote the manuscript. B.S., K.K., Y.H., Y.N., Y.F. and LT.T. participated in the experimental work and collected and analyzed data. B.S. and M.S. contributed to the study design, supervised the study, and commented on the manuscript. All authors have read and approved the final version of the manuscript.

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Authors and Affiliations

  1. Laboratory of Nutrition Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, 812-8581, Japan

    Bungo Shirouchi, Kentaro Kashima, Yasutaka Horiuchi, Yuki Nakamura, Yumiko Fujimoto, Li-Tao Tong & Masao Sato

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  1. Bungo Shirouchi
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  2. Kentaro Kashima
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  3. Yasutaka Horiuchi
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  4. Yuki Nakamura
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  5. Yumiko Fujimoto
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  6. Li-Tao Tong
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  7. Masao Sato
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Correspondence to Masao Sato.

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Shirouchi, B., Kashima, K., Horiuchi, Y. et al. 27-Hydroxycholesterol suppresses lipid accumulation by down-regulating lipogenic and adipogenic gene expression in 3T3-L1 cells. Cytotechnology 69, 485–492 (2017). https://doi.org/10.1007/s10616-016-9962-5

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