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Adiponectin receptor 1 enhances fatty acid metabolism and cell survival in palmitate-treated HepG2 cells through the PI3 K/AKT pathway

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Abstract

Purposes

Hepatic lipid overloading induces lipotoxicity which can cause hepatocyte damage, fibrosis, and eventually progress to cirrhosis, which is associated with nonalcoholic fatty liver disease. Adiponectin receptors play important roles in regulating lipid metabolism. In this study, we used a lentivirus system to overexpress the adiponectin receptor 1 (AdipoR1) in HepG2 cells to define the role of adiponectin and its receptor 1 in the development of fatty liver syndrome.

Methods and results

Exposure of human hepatocytes, HepG2 cells, to palmitate (0.2 or 0.4 mM) for 16 h resulted in elevated apoptosis, whereas AdipoR1 decreased the palmitate-induced apoptosis. Transgene AdipoR1 increased the expression of FATP2, acyl-coA oxidase, and carnitine palmitoyltransferase I in palmitate-treated HepG2 cells. The transcript level of acetyl-CoA carboxylase and fatty acid synthase was upregulated by palmitate treatment, while AdipoR1 reversed the effect induced by palmitate. AdipoR1 increased the gene expression of cytochrome C oxidase, peroxisome proliferator-activated receptor α, and decreased the gene expression of PGC1α and AMPKα in HepG2 cells under palmitate treatment. Palmitate suppressed ATP production, while transgene AdipoR1 reversed the decreased ATP production by palmitate. Transgene AdipoR1 enhanced AKT phosphorylation in HepG2 cells both with and without palmitate treatment. When PI3 kinase inhibitor was applied, the protective effect of AdipoR1 was absent, such that palmitate again decreased ATP production while also reducing cell viability.

Conclusion

AdipoR1 enhances fatty acid metabolism and cell viability in palmitate-treated HepG2 cells partially by activating AKT signaling. Therefore, AdipoR1 has therapeutic potential in the treatment of nonalcoholic fatty liver disease.

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Acknowledgments

The authors would like to express our gratitude to the laboratory members for their help and input during the study. This study was supported in part by a Grant (102R7615-3) from National Taiwan University and Grants (NSC 99-2313-B-002-031 and NSC 101-2313-B-002-030-MY3) from the National Science Council in Taiwan.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Animal Science and Technology, National Taiwan University, 50, Lane 155, Sec 3, Keelung Rd, Taipei, 112, Taiwan

    I-Pin Chou, Yuan Yu Lin, Shih-Torng Ding & Ching-Yi Chen

  2. Institute of Biotechnology, National Taiwan University, No. 50, Lane 155, Sec 3 Keelung Rd, Taipei, Taiwan

    Shih-Torng Ding

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  1. I-Pin Chou
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  2. Yuan Yu Lin
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Correspondence to Ching-Yi Chen.

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Chou, IP., Lin, Y.Y., Ding, ST. et al. Adiponectin receptor 1 enhances fatty acid metabolism and cell survival in palmitate-treated HepG2 cells through the PI3 K/AKT pathway. Eur J Nutr 53, 907–917 (2014). https://doi.org/10.1007/s00394-013-0594-7

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  • DOI: https://doi.org/10.1007/s00394-013-0594-7

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