Cytotechnology

, Volume 69, Issue 3, pp 485–492 | Cite as

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

  • Bungo Shirouchi
  • Kentaro Kashima
  • Yasutaka Horiuchi
  • Yuki Nakamura
  • Yumiko Fujimoto
  • Li-Tao Tong
  • Masao Sato
JAACT Special Issue
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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.

Keywords

27-Hydroxycholesterol LXRα PPARγ Lipid accumulation 3T3-L1 adipocytes 
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Notes

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.

Compliance with ethical standards

Conflict of interest

None.

References

  1. American Institute of Nutrition (1977) Report of the American Institute of Nurtition ad hoc Committee on Standards for Nutritional Studies. J Nutr 107:1340–1348Google Scholar
  2. Ando M, Tomoyori H, Imaizumi K (2002) Dietary cholesterol-oxidation products accumulate in serum and liver in apolipoprotein E-deficient mice, but do not accelerate atherosclerosis. Br J Nutr 88:339–345CrossRefGoogle Scholar
  3. Bikle D (2001) Vitamin D regulation of immune function. In: Litwack G (ed) Vitamins and the immune system, vol 86. Elsevier, Amsterdam, pp 1–21CrossRefGoogle Scholar
  4. Björkhem I, Diczfalusy U (2002) Oxysterols: friends, foes, or just fellow passengers? Arterioscler Thromb Vasc Biol 22:734–742CrossRefGoogle Scholar
  5. Chirgwin JM, Przbyla AE, McDonald RJ, Rutter WJ (1979) Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18:5294–5299CrossRefGoogle Scholar
  6. Granlund L, Pedersen JI, Nebb HI (2005) Impaired lipid accumulation by trans10, cis12 CLA during adipocyte differentiation is dependent on timing and length of treatment. Biochim Biophys Acta 1687:11–22CrossRefGoogle Scholar
  7. Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ (1996) An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 383:728–731CrossRefGoogle Scholar
  8. Joseph SB, Laffitte BA, Patel PH, Watson MA, Matsukuma KE, Walczak R, Collins JL, Osborne TF, Tontonoz P (2002) Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors. J Biol Chem 277:11019–11025CrossRefGoogle Scholar
  9. Juvet LK, Andresen SM, Schuster GU, Dalen KT, Tobin KA, Hollung K, Haugen F, Jacinto S, Ulven SM, Bamberg K, Gustafsson JA, Nebb HI (2003) On the role of liver X receptors in lipid accumulation in adipocytes. Mol Endocrinol 17:172–182CrossRefGoogle Scholar
  10. Kim JB, Spiegelman BM (1996) ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Dev 10:1096–1107CrossRefGoogle Scholar
  11. Laurencikiene J, Rydén M (2012) Liver X receptors and fat cell metabolism. Int J Obes (Lond) 36:1494–1502CrossRefGoogle Scholar
  12. Lee J, Lee J, Jung E, Kim YS, Roh K, Jung KH, Park D (2010) Ultraviolet A regulates adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells via up-regulation of Kruppel-like factor 2. J Biol Chem 285:32647–32656CrossRefGoogle Scholar
  13. Lefterova MI, Zhang Y, Steger DJ, Schupp M, Schug J, Cristancho A, Feng D, Zhuo D, Stoeckert CJ Jr, Liu XS, Lazar MA (2008) PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale. Genes Dev 22:2941–2952CrossRefGoogle Scholar
  14. Li J, Daly E, Campioli E, Wabitsch M, Papadopoulos V (2014) De novo synthesis of steroids and oxysterols in adipocytes. J Biol Chem 289:747–764CrossRefGoogle Scholar
  15. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
  16. Matsuoka R, Shirouchi B, Kawamura S, Baba S, Shiratake S, Nagata K, Imaizumi K, Sato M (2014) Dietary egg white protein inhibits lymphatic lipid transport in thoracic lymph duct-cannulated rats. J Agric Food Chem 62:10694–10700CrossRefGoogle Scholar
  17. Matsuzawa Y (2006) Therapy Insight: adipocytokines in metabolic syndrome and related cardiovascular disease. Nat Clin Pract Cardiovasc Med 3:35–42CrossRefGoogle Scholar
  18. Schroepfer GJ Jr (2000) Oxysterols: modulators of cholesterol metabolism and other processes. Physiol Rev 80:361–554Google Scholar
  19. Schultz JR, Tu H, Luk A, Repa JJ, Medina JC, Li L, Schwendner S, Wang S, Thoolen M, Mangelsdorf DJ, Lustig KD, Shan B (2000) Role of LXRs in control of lipogenesis. Genes Dev 14:2831–2838CrossRefGoogle Scholar
  20. Sottero B, Gamba P, Gargiulo S, Leonarduzzi G, Poli G (2009) Cholesterol oxidation products and disease: an emerging topic of interest in medicinal chemistry. Curr Med Chem 16:685–705CrossRefGoogle Scholar
  21. Willy PJ, Umesono K, Ong ES, Evans RM, Heyman RA, Mangelsdorf DJ (1995) LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev 9:1033–1045CrossRefGoogle Scholar
  22. Yanai H (2011) Statcel 3—the usefull add-in software forms on Excel, 3rd edn. OMS, TokyoGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Bungo Shirouchi
    • 1
  • Kentaro Kashima
    • 1
  • Yasutaka Horiuchi
    • 1
  • Yuki Nakamura
    • 1
  • Yumiko Fujimoto
    • 1
  • Li-Tao Tong
    • 1
  • Masao Sato
    • 1
  1. 1.Laboratory of Nutrition Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate SchoolKyushu UniversityFukuokaJapan

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