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Lack of enzyme promotes fatty liver disease in thin patients

Non-alcoholic fatty liver disease – steatohepatitis – is an increasingly common chronic form of hepatitis. As Jun Wada and colleagues at Okayama University Graduate School of Medicine, Shigei Medical Research Institute and Dainippon Sumitomo Pharma explain in a recent report, “Although obesity is undoubtedly one of the main risk factors for the development of non-alcoholic fatty liver disease, many clinical observations demonstrated the presence of lean NAFLD patients with normal body mass index (BMI).” The team’s latest work shows that absence of the enzyme phosphatidylethanolamine N-methyltransferase (PEMT), while protecting from diet-induced obesity and diabetes, leads to the prominent development of fatty liver disease and tumours in response to a high-fat high-sucrose diet.

PEMT catalyses methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) in liver cells using S-adenosyl methionine as a methyl donor. The ratio of PE to PC is known to be crucial to cell membrane integrity and resistance to endoplasmic reticulum stress and the infiltration of the liver with fat.

liver tissues
Phenotype of Pemt+/+, Pemt+/- and Pemt -/- mice under high fat-high sucrose (HFHS) diet at 60 weeks of age. (a-c) Gross appearance of liver. Bar = 1 cm. Regenerative nodules and adenoma are indicated by arrow heads (c). (d-f) Masson-Trichrome staining of liver tissues. Bar = 100 ? m.
Image: Okayama University