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

Theranostics
Chao ZhangDonggang Xu

Abstract

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-fedApoE-/-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 bothin vivoandin 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 "ign...Continue Reading

Citations

Apr 20, 2017·International Journal of Molecular Sciences·Chao ZhangDonggang Xu

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Datasets Mentioned

BETA
GSE88964

Methods Mentioned

BETA
chips
MDA
ELISA
flow cytometry
immunoprecipitation
PCR

Software Mentioned

R analysis WGCNA
Wikipathways
R
WGCNA
RankProd
GEne SeT AnaLysis Toolkit ( WebGestalt )

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