Theranostics 2017; 7(6):1749-1769. doi:10.7150/thno.18415 This issue Cite

Research Paper

SAK-HV Triggered a Short-period Lipid-lowering Biotherapy Based on the Energy Model of Liver Proliferation via a Novel Pathway

Chao Zhang, Zhiguang Huang, Haoran Jing, Wenliang Fu, Min Yuan, Wenrong Xia, Ling Cai, Xiangdong Gan, Yao Chen, Minji Zou, Minhui Long, Jiaxi Wang, Min Wang*✉, Donggang Xu*✉

Laboratory of Genome Engineering, Beijing Institute of Basic Medical Sciences, Beijing, PR China.
*These authors share corresponding authorship.

Citation:
Zhang C, Huang Z, Jing H, Fu W, Yuan M, Xia W, Cai L, Gan X, Chen Y, Zou M, Long M, Wang J, Wang M, Xu D. SAK-HV Triggered a Short-period Lipid-lowering Biotherapy Based on the Energy Model of Liver Proliferation via a Novel Pathway. Theranostics 2017; 7(6):1749-1769. doi:10.7150/thno.18415. https://www.thno.org/v07p1749.htm
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Abstract

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The accumulations of excess lipids within liver and serum are defined as non-alcoholic fatty liver disease (NAFLD) and hyperlipemia respectively. Both of them are components of metabolic syndrome that greatly threaten human health. Here, a recombinant fusion protein (SAK-HV) effectively treated NAFLD and hyperlipemia in high-fat-fed ApoE-/- mice, quails and rats within just 14 days. Its triglyceride and cholesterol-lowering effects were significantly better than that of atorvastatin during the observation period. We explored the lipid-lowering mechanism of SAK-HV by the hepatic transcriptome analysis and serials of experiments both in vivo and in vitro. Unexpectedly, SAK-HV triggered a moderate energy and material-consuming liver proliferation to dramatically decrease the lipids from both serum and liver. We provided the first evidence that PGC-1α mediated the hepatic synthesis of female hormones during liver proliferation, and proposed the complement system-induced PGC-1α-estrogen axis via the novel STAT3-C/EBPβ-PGC-1α pathway in liver as a new energy model for liver proliferation. In this model, PGC-1α ignited and fueled hepatocyte activation as an “igniter”; PGC-1α-induced estrogen augmented the energy supply of PGC-1α as an “ignition amplifier”, then triggered the hepatocyte state transition from activation to proliferation as a “starter”, causing triglyceride and cholesterol-lowering effects via PPARα-mediated fatty acid oxidation and LDLr-mediated cholesterol uptake, respectively. Collectively, the SAK-HV-triggered distinctive lipid-lowering strategy based on the new energy model of liver proliferation has potential as a novel short-period biotherapy against NAFLD and hyperlipemia.

Keywords: non-alcoholic fatty liver disease (NAFLD), hyperlipemia, liver proliferation, PGC-1α, estrogen, biotherapy.


Citation styles

APA
Zhang, C., Huang, Z., Jing, H., Fu, W., Yuan, M., Xia, W., Cai, L., Gan, X., Chen, Y., Zou, M., Long, M., Wang, J., Wang, M., Xu, D. (2017). SAK-HV Triggered a Short-period Lipid-lowering Biotherapy Based on the Energy Model of Liver Proliferation via a Novel Pathway. Theranostics, 7(6), 1749-1769. https://doi.org/10.7150/thno.18415.

ACS
Zhang, C.; Huang, Z.; Jing, H.; Fu, W.; Yuan, M.; Xia, W.; Cai, L.; Gan, X.; Chen, Y.; Zou, M.; Long, M.; Wang, J.; Wang, M.; Xu, D. SAK-HV Triggered a Short-period Lipid-lowering Biotherapy Based on the Energy Model of Liver Proliferation via a Novel Pathway. Theranostics 2017, 7 (6), 1749-1769. DOI: 10.7150/thno.18415.

NLM
Zhang C, Huang Z, Jing H, Fu W, Yuan M, Xia W, Cai L, Gan X, Chen Y, Zou M, Long M, Wang J, Wang M, Xu D. SAK-HV Triggered a Short-period Lipid-lowering Biotherapy Based on the Energy Model of Liver Proliferation via a Novel Pathway. Theranostics 2017; 7(6):1749-1769. doi:10.7150/thno.18415. https://www.thno.org/v07p1749.htm

CSE
Zhang C, Huang Z, Jing H, Fu W, Yuan M, Xia W, Cai L, Gan X, Chen Y, Zou M, Long M, Wang J, Wang M, Xu D. 2017. SAK-HV Triggered a Short-period Lipid-lowering Biotherapy Based on the Energy Model of Liver Proliferation via a Novel Pathway. Theranostics. 7(6):1749-1769.

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