The role of Hepassocin in the development of non-alcoholic fatty liver disease

Hung Tsung Wu, Feng Hwa Lu, Horng Yih Ou, Yu Chu Su, Hao Chang Hung, Jin Shang Wu, Yi Ching Yang, Chao Liang Wu, Chih Jen Chang

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)


Background & Aims While non-alcoholic fatty liver disease (NAFLD) is the most common risk factor of chronic liver disease, the mechanisms that initiate its development are obscure. Hepassocin (HPS) is a hepatokine that has been reported to be involved in liver regeneration. In addition to the mitogenic activity of HPS, HPS expression is decreased in patients with hepatoma. However, the role of HPS in NAFLD is still unknown. Methods A total of 393 subjects with (n = 194) or without (n = 199) NAFLD were enrolled to evaluate the serum HPS concentration. In order to clarify the causal inference between HPS and NAFLD, we used experimental animal and cell models. Hepatic overexpression or silencing of HPS was achieved by lentiviral vector delivery in mice and lipofectamine transfection in HepG2 cells. Lipogenesis related proteins were detected by Western blots. The expression of inflammatory factors was determined by real-time polymerase chain reaction. Results Subjects with NAFLD had a higher serum HPS concentration than those without it. Overexpression of HPS increased hepatic lipid accumulation and NAFLD activity scores (NAS), whereas deletion of HPS improved high fat diet-induced hepatic steatosis and decreased NAS in mice. Additionally, oleic acid, a steatogenic reagent, increased HPS expression in hepatocytes. Furthermore, overexpression of HPS in HepG2 cells induced lipid accumulation through an extracellular signal-regulated kinase 1/2 (ERK1/2)-dependent pathway, whereas deletion of HPS decreased oleic acid-induced lipid accumulation. Conclusions The present study provides evidence that HPS plays an important role in NAFLD and induces hepatic lipid accumulation through an ERK1/2-dependent pathway.

Original languageEnglish
Pages (from-to)1065-1072
Number of pages8
JournalJournal of Hepatology
Issue number5
Publication statusPublished - Nov 1 2013
Externally publishedYes


  • Fatty acids
  • Hepatic steatosis
  • Liver
  • Oleic acid
  • STAT3

ASJC Scopus subject areas

  • Hepatology


Dive into the research topics of 'The role of Hepassocin in the development of non-alcoholic fatty liver disease'. Together they form a unique fingerprint.

Cite this