Non-alcoholic fatty liver disease (NAFLD)
Extensive build-up of fat in the liver is responsible for a range of diseases including simple steatosis and non-alcoholic steatohepatitis (NASH). The increased instances of NAFLD are linked with the rise in obesity and diabetes, which are now considered to have reached epidemic proportions. However, NASH has also been reported in patients with a normal body mass index (BMI), and the prevalence of “lean NAFLD” was recently reported at 12% in Greece, 20% in India and 15% in China.
Mice fed a methionine- and choline-deficient diet (MCD) are a widely used mouse models for NASH research. An absence of obesity and insulin resistance has been observed in both MCD mice and PEMT knockout mice fed high-fat high-sucrose diets.
The genome-wide sequencing-based DNA methylation analysis by the researchers revealed enhanced methylation of two genes associated with cyclin D1 degradation and negative regulation. These results implicate the upregulation of cyclin D1 in the development of liver disease and tumours in PEMT knock-out mice.
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 μ m.
Atsuko Nakatsuka, Makoto Matsuyama, Satoshi Yamaguchi, Akihiro Katayama, Jun Eguch, Kazutoshi Murakami, Sanae Teshigawara, Daisuke Ogawa, Nozomu Wada, Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Eijiro Watanabe & Jun Wada. Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis, Scientific Reports 6 21721 (2016).