Mitochondrial dysfunction is induced by the overexpression of UCP4 in 3T3-L1 adipocytes

  • Authors:
    • Chun-Lin Gao
    • Jin-Gai Zhu
    • Ya-Ping Zhao
    • Xiao-Hui Chen
    • Chen-Bo Ji
    • Chun-Mei Zhang
    • Chun Zhu
    • Zheng-Kun Xia
    • Yu-Zhu Peng
    • Xi-rong Guo
  • View Affiliations

  • Published online on: January 1, 2010     https://doi.org/10.3892/ijmm_00000315
  • Pages: 71-80
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Abstract

Uncoupling proteins (UCPs) belong to a superfamily of mitochondrial transporters that uncouple ATP synthesis from electron transport. We have previously shown that uncoupling protein 4 (UCP4) is differentially expressed in omental adipose tissue in diet-induced obese and normal rats. Overexpression of UCP4 promotes proliferation and inhibits apoptosis and differentiation of preadipocytes. In this work, we further characterized the effect of UCP4 on mitochondrial function in mature 3T3-L1 adipocytes. Transmission electron microscopy (TEM) showed that adipocytes overexpressing UCP4 displayed condensed mitochondria with twisted, condensed, and unclear cristae. Moreover, the loss of the mitochondrial membrane potential and intramitochondrial calcium was found. The adipocytes overexpressing UCP4 also showed decreased mitochondrial copy number (mtDNA) and lower mRNA expression of key factors in mitochondrial biogenesis, including PGC-1α and mtTFA. NRF-1 and ERRβ levels were down-regulated, while NRF-2 levels were upregulated. In addition, UCP4 overexpression impaired mitochondrial fusion and fission, as indicated by decreased mitofusin mfn1, mfn2, and mitofission DRP1. When it came to total adipocytes, the UCP4 overexpressing adipocytes showed higher production reactive oxygen species and diminished levels of intracellular ATP. Furthermore, overexpression of UCP4 brought about impaired insulin sensitivity in adipocytes. UCP4 plays an important role in mitochondrial function and adipocyte insulin resistance. Its function deserves further attention.

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January 2010
Volume 25 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Gao C, Zhu J, Zhao Y, Chen X, Ji C, Zhang C, Zhu C, Xia Z, Peng Y, Guo X, Guo X, et al: Mitochondrial dysfunction is induced by the overexpression of UCP4 in 3T3-L1 adipocytes. Int J Mol Med 25: 71-80, 2010.
APA
Gao, C., Zhu, J., Zhao, Y., Chen, X., Ji, C., Zhang, C. ... Guo, X. (2010). Mitochondrial dysfunction is induced by the overexpression of UCP4 in 3T3-L1 adipocytes. International Journal of Molecular Medicine, 25, 71-80. https://doi.org/10.3892/ijmm_00000315
MLA
Gao, C., Zhu, J., Zhao, Y., Chen, X., Ji, C., Zhang, C., Zhu, C., Xia, Z., Peng, Y., Guo, X."Mitochondrial dysfunction is induced by the overexpression of UCP4 in 3T3-L1 adipocytes". International Journal of Molecular Medicine 25.1 (2010): 71-80.
Chicago
Gao, C., Zhu, J., Zhao, Y., Chen, X., Ji, C., Zhang, C., Zhu, C., Xia, Z., Peng, Y., Guo, X."Mitochondrial dysfunction is induced by the overexpression of UCP4 in 3T3-L1 adipocytes". International Journal of Molecular Medicine 25, no. 1 (2010): 71-80. https://doi.org/10.3892/ijmm_00000315