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Human adenovirus 36 decreases fatty acid oxidation and increases de novo lipogenesis in primary cultured human skeletal muscle cells by promoting Cidec/FSP27 expression

International Journal of Obesity volume 34, pages 1355–1364 (2010)Cite this article

Subjects

Abstract

Background:

It has been well documented that human adenovirus type 36 (Ad-36) is associated with obesity. However, the underlying molecular mechanism of Ad-36 inducing obesity remains unknown. We sought to investigate the effect of Ad-36 infection on Cidec, AMPK pathway and lipid metabolism in primary cultured human skeletal muscle cells.

Methods:

Cidec/fat-specific protein 27 (FSP27), fatty acid oxidation, AMPK signaling and the abundance of proteins involved in lipid synthesis were determined in muscle cells infected with various doses (1.9–7.6 MOI) of Ad-36 and non-lipogenic adenovirus type 2 (Ad-2) as a negative control as well as an uninfected control. Cidec/FSP27 siRNA transfection was performed in Ad-36-infected muscle cells.

Results:

Our data show that Ad-36 significantly reduced fatty acid oxidation in a dose-dependent manner (all P values are <0.01), but Ad-2 did not affect fatty acid oxidation. Ad-36 substantially increased Cidec/FSP27, ACC, sterol regulatory element-binding protein 1c (SREBP-1c), SREBP-2 and 3-hydroxy-3-methylglutaryl-CoA reductase protein abundance, but significantly reduced AMPK activity, mitochondrial mass and uncoupling protein 3 (UCP3) abundance in comparison with control cells (all P values are <0.01). Oil Red O staining revealed that there was substantial fat accumulation in the Ad-36-infected muscle cells. Furthermore, Cidec/FSP27 siRNA transfection significantly reduced FSP27 expression and partially restored AMPK signaling, increased UCP3 and decreased SERBP 1c and perilipin proteins in Ad-36-infected muscle cells. Interestingly, neither Ad-36 nor Ad-2 affected peroxisome proliferator-activated receptor γ protein expression in muscle cells.

Conclusion:

This study suggests that Ad-36 induced lipid droplets in the cultured skeletal muscle cells and this process may be mediated by promoting Cidec/FSP27 expression.

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Abbreviations

SREBP-1c:

sterol regulatory element-binding protein 1c

HMGR:

3-hydroxy-3-methylglutaryl-CoA reductase

UCP3:

uncoupling protein 3.

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Acknowledgements

We thank Dr Nikhil Dhurandhar for kindly providing adenovirus 2 and adenovirus 36. This project used facilities that are supported in part by COBRE (NIH P20-RR021945) and CNRU (NIH 1P30-DK072476) center grants from the National Institutes of Health.

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Authors and Affiliations

  1. Diabetes and Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA

    Z Q Wang, Y Yu, X H Zhang, E Z Floyd & W T Cefalu

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  1. Z Q Wang
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Correspondence to Z Q Wang.

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Wang, Z., Yu, Y., Zhang, X. et al. Human adenovirus 36 decreases fatty acid oxidation and increases de novo lipogenesis in primary cultured human skeletal muscle cells by promoting Cidec/FSP27 expression. Int J Obes 34, 1355–1364 (2010). https://doi.org/10.1038/ijo.2010.77

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