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The role of hepassocin in the development of non-alcoholic fatty liver disease.
J Hepatol. 2013 Nov; 59(5):1065-72.JH

Abstract

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.

Authors+Show Affiliations

Research Center of Herbal Medicine, New Drugs, and Nutritional Supplements, National Cheng Kung University, Taiwan; Department of Family Medicine, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23792031

Citation

Wu, Hung-Tsung, et al. "The Role of Hepassocin in the Development of Non-alcoholic Fatty Liver Disease." Journal of Hepatology, vol. 59, no. 5, 2013, pp. 1065-72.
Wu HT, Lu FH, Ou HY, et al. The role of hepassocin in the development of non-alcoholic fatty liver disease. J Hepatol. 2013;59(5):1065-72.
Wu, H. T., Lu, F. H., Ou, H. Y., Su, Y. C., Hung, H. C., Wu, J. S., Yang, Y. C., Wu, C. L., & Chang, C. J. (2013). The role of hepassocin in the development of non-alcoholic fatty liver disease. Journal of Hepatology, 59(5), 1065-72. https://doi.org/10.1016/j.jhep.2013.06.004
Wu HT, et al. The Role of Hepassocin in the Development of Non-alcoholic Fatty Liver Disease. J Hepatol. 2013;59(5):1065-72. PubMed PMID: 23792031.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of hepassocin in the development of non-alcoholic fatty liver disease. AU - Wu,Hung-Tsung, AU - Lu,Feng-Hwa, AU - Ou,Horng-Yih, AU - Su,Yu-Chu, AU - Hung,Hao-Chang, AU - Wu,Jin-Shang, AU - Yang,Yi-Ching, AU - Wu,Chao-Liang, AU - Chang,Chih-Jen, Y1 - 2013/06/18/ PY - 2013/02/22/received PY - 2013/05/23/revised PY - 2013/06/10/accepted PY - 2013/6/25/entrez PY - 2013/6/26/pubmed PY - 2014/10/1/medline KW - ACC-1 KW - ERK1/2 KW - FAS KW - FFAs KW - Fatty acids KW - HCC KW - HFD KW - HNF-1 KW - HPS KW - Hepatic steatosis KW - Liver KW - NAFLD KW - NAFLD activity score KW - NAS KW - NASH KW - OA KW - Oleic acid KW - SREBP-1 KW - STAT3 KW - acetyl-CoA carboxylase-1 KW - extracellular signal-regulated kinase 1/2 KW - fatty acid synthase KW - free fatty acids KW - hepassocin KW - hepatocellular carcinoma KW - hepatocyte nuclear factor-1 KW - high fat diet KW - non-alcoholic fatty liver disease KW - non-alcoholic steatohepatitis KW - oleic acid KW - signal transducer and activator of transcription 3 KW - sterol regulatory element-binding protein-1 SP - 1065 EP - 72 JF - Journal of hepatology JO - J Hepatol VL - 59 IS - 5 N2 - 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. SN - 1600-0641 UR - https://www.unboundmedicine.com/medline/citation/23792031/The_role_of_hepassocin_in_the_development_of_non_alcoholic_fatty_liver_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-8278(13)00414-5 DB - PRIME DP - Unbound Medicine ER -