Insufficiency of Phosphatidylethanolamine N-Methyltransferase is Risk for Lean Non-Alcoholic Steatohepatitis
May 13, 2016
Non-alcoholic fatty liver disease (NAFLD) has been widely recognized as an important manifestation of metabolic syndrome. The development of non-alcoholic steatohepatitis (NASH) is closely related to the obesity and diabetes mellitus. Although obesity is one of the main risk factors for the development of NAFLD and NASH, many clinical observations showed the presence of NASH patients with normal body mass index (BMI).
Dr. Wada, Dr. Nakatsuka, and their colleagues demonstrated that insufficiency of Phosphatidylethanolamine N-Methyltransferase (PEMT) is a risk for the lean NASH.
The findings were published online February 17, 2016 in the journal of Scientific Reports.
http://www.nature.com/articles/srep21721
The research group fed the PEMT deficit mice with high fat-high sucrose diet. While protected from diet-induced obesity and diabetes mellitus, the mice developed prominent steatohepatitis and multiple liver tumors. In addition, the group found that PEMT mRNA expression in liver tissues of NASH patients was significantly lower than that of patients with simple steatosis.
Furthermore, it was demonstrated that the deficiency of PEMT enhanced apoptosis and developed inflammation, and also promoted DNA methylation and reduced mRNA expression of Fbxo31 and HNF4α in the liver of the PEMT deficient mice.
The findings could lead to the development of diagnostic tools for pre-onset steatohepatitis, for example, by measuring the quantity of PEMT in liver tissues or blood cells or by checking the presence of single nucleotide polymorphisms on PEMT genes. In addition, it is possible to advance the research to develop innovative therapies for NASH.
Contact information
Mototaka Senda, Ph.D.
Director, Okayama University Silicon Valley Office
Organization for research Promotion and Collaboration, Okayama University
2450 Peralta Blvd. #222
Fremont, CA 94536
Jun Wada M.D.,Ph.D.
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University