%0 Journal Article
%T SAK-HV Triggered a Short-period Lipid-lowering Biotherapy Based on the Energy Model of Liver Proliferation via a Novel Pathway
%A Chao Zhang
%A Donggang Xu
%A Haoran Jing
%A Jiaxi Wang
%A Ling Cai
%A Min Wang
%A Min Yuan
%A Minhui Long
%A Minji Zou
%A Wenliang Fu
%A Wenrong Xia
%A Xiangdong Gan
%A Yao Chen
%A Zhiguang Huang
%J Theranostics
%D 2017
%I Ivyspring International Publisher
%R 10.7150/thno.18415
%X 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-1¦Á mediated the hepatic synthesis of female hormones during liver proliferation, and proposed the complement system-induced PGC-1¦Á-estrogen axis via the novel STAT3-C/EBP¦Â-PGC-1¦Á pathway in liver as a new energy model for liver proliferation. In this model, PGC-1¦Á ignited and fueled hepatocyte activation as an ¡°igniter¡±; PGC-1¦Á-induced estrogen augmented the energy supply of PGC-1¦Á as an ¡°ignition amplifier¡±, then triggered the hepatocyte state transition from activation to proliferation as a ¡°starter¡±, causing triglyceride and cholesterol-lowering effects via PPAR¦Á-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.
%K non-alcoholic fatty liver disease (NAFLD)
%K hyperlipemia
%K liver proliferation
%K PGC-1¦Á
%K estrogen
%K biotherapy.
%U http://www.thno.org/v07p1749.htm