Loss of glycine n-methyltransferase associates with angiopoietin-like protein 8 expression in high fat-diet-fed mice

Jian Wei Huang, Chao Ju Chen, Chia Hung Yen, Yi Ming Arthur Chen, Yu Peng Liu

Research output: Contribution to journalArticle

Abstract

Imbalance of lipid metabolism is a main cause of metabolic syndrome leading to life-threatening metabolic diseases. Angiopoietin-like protein 8 (Angptl8) was recently identified as a liver and adipose tissue-released hormone that is one of the molecules involved in triglyceride metabolism. However, the regulatory mechanism of Angptl8 is largely unknown. A high fat diet (HFD)-fed mouse model, which showed high cholesterol, high triglyceride, and high insulin in the blood, revealed the upregulation of hepatic and plasma Angptl8 and the downregulation of hepatic glycine N-methyltransferase (GNMT). The inverse correlation of hepatic Angptl8 and GNMT expression in the livers of HFD-fed mice was also confirmed in a publicly available microarray dataset. The mechanistic study using primary hepatocytes showed that the Angptl8 expression could be induced by insulin treatment in a dose-and time-dependent manner. Inhibition of PI3K/Akt pathway by the specific inhibitors or the dominant-negative Akt blocked the insulin-induced Angptl8 expression. Moreover, knockout of GNMT promoted the Akt activation as well as the Angptl8 expression. These results suggested that GNMT might be involved in insulin-induced Angptl8 expression in HFD-mediated metabolic syndrome.

Original languageEnglish
Article number4223
JournalInternational Journal of Molecular Sciences
Volume20
Issue number17
DOIs
Publication statusPublished - Sep 1 2019

Keywords

  • Angiopoietin-like protein 8
  • Glycine N-methyltransferase
  • High fat diet
  • Insulin
  • Metabolic syndrome

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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