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Loss of Glycine N-Methyltransferase Associates with Angiopoietin-Like Protein 8 Expression in High Fat-Diet-Fed Mice

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,...

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Autores principales: Huang, Jian-Wei, Chen, Chao-Ju, Yen, Chia-Hung, Chen, Yi-Ming Arthur, Liu, Yu-Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747252/
https://www.ncbi.nlm.nih.gov/pubmed/31470507
http://dx.doi.org/10.3390/ijms20174223
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author Huang, Jian-Wei
Chen, Chao-Ju
Yen, Chia-Hung
Chen, Yi-Ming Arthur
Liu, Yu-Peng
author_facet Huang, Jian-Wei
Chen, Chao-Ju
Yen, Chia-Hung
Chen, Yi-Ming Arthur
Liu, Yu-Peng
author_sort Huang, Jian-Wei
collection PubMed
description 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.
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spelling pubmed-67472522019-09-27 Loss of Glycine N-Methyltransferase Associates with Angiopoietin-Like Protein 8 Expression in High Fat-Diet-Fed Mice Huang, Jian-Wei Chen, Chao-Ju Yen, Chia-Hung Chen, Yi-Ming Arthur Liu, Yu-Peng Int J Mol Sci Article 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. MDPI 2019-08-29 /pmc/articles/PMC6747252/ /pubmed/31470507 http://dx.doi.org/10.3390/ijms20174223 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huang, Jian-Wei
Chen, Chao-Ju
Yen, Chia-Hung
Chen, Yi-Ming Arthur
Liu, Yu-Peng
Loss of Glycine N-Methyltransferase Associates with Angiopoietin-Like Protein 8 Expression in High Fat-Diet-Fed Mice
title Loss of Glycine N-Methyltransferase Associates with Angiopoietin-Like Protein 8 Expression in High Fat-Diet-Fed Mice
title_full Loss of Glycine N-Methyltransferase Associates with Angiopoietin-Like Protein 8 Expression in High Fat-Diet-Fed Mice
title_fullStr Loss of Glycine N-Methyltransferase Associates with Angiopoietin-Like Protein 8 Expression in High Fat-Diet-Fed Mice
title_full_unstemmed Loss of Glycine N-Methyltransferase Associates with Angiopoietin-Like Protein 8 Expression in High Fat-Diet-Fed Mice
title_short Loss of Glycine N-Methyltransferase Associates with Angiopoietin-Like Protein 8 Expression in High Fat-Diet-Fed Mice
title_sort loss of glycine n-methyltransferase associates with angiopoietin-like protein 8 expression in high fat-diet-fed mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747252/
https://www.ncbi.nlm.nih.gov/pubmed/31470507
http://dx.doi.org/10.3390/ijms20174223
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