Vagus nerve contributes to the development of steatohepatitis and obesity in phosphatidylethanolamine N-methyltransferase deficient mice.

Abstract

BACKGROUND & AIMS:

Phosphatidylethanolamine N-methyltransferase (PEMT), a liver enriched enzyme, is responsible for approximately one third of hepatic phosphatidylcholine biosynthesis. When fed a high-fat diet (HFD), Pemt(-/-) mice are protected from HF-induced obesity; however, they develop steatohepatitis. The vagus nerve relays signals between liver and brain that regulate peripheral adiposity and pancreas function. Here we explore a possible role of the hepatic branch of the vagus nerve in the development of diet induced obesity and steatohepatitis in Pemt(-/-) mice.

METHODS:

8-week old Pemt(-/-) and Pemt(+/+) mice were subjected to hepatic vagotomy (HV) or capsaicin treatment, which selectively disrupts afferent nerves, and were compared to sham-operated or vehicle-treatment, respectively. After surgery, mice were fed a HFD for 10 weeks.

RESULTS:

HV abolished the protection against the HFD-induced obesity and glucose intolerance in Pemt(-/-) mice. HV normalized phospholipid content and prevented steatohepatitis in Pemt(-/-) mice. Moreover, HV increased the hepatic anti-inflammatory cytokine interleukin-10, reduced chemokine monocyte chemotactic protein-1 and the ER stress marker C/EBP homologous protein. Furthermore, HV normalized the expression of mitochondrial electron transport chain proteins and of proteins involved in fatty acid synthesis, acetyl-CoA carboxylase and fatty acid synthase in Pemt(-/-) mice. However, disruption of the hepatic afferent vagus nerve by capsaicin failed to reverse either the protection against the HFD-induced obesity or the development of HF-induced steatohepatitis in Pemt(-/-) mice.

CONCLUSIONS:

Neuronal signals via the hepatic vagus nerve contribute to the development of steatohepatitis and protection against obesity in HFD fed Pemt(-/-) mice.

• Authors: Xia Gao, Jelske N van der Veen, Linfu Zhu, Todd Chaba, Marta Ordoñez, Susanne Lingrell, Debby P Y Koonen, Jason R B Dyck, Antonio Gomez-Muñoz, Dennis E Vance, René L Jacobs
• Journal: Journal of hepatology (J Hepatol) Vol. 62 Issue 4 Pg. 913-20 (Apr 2015) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 25433161 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• Chemokine CCL2
• Phosphatidylcholines
• Interleukin-10
• Transcription Factor CHOP
• PEMT protein, mouse
• Phosphatidylethanolamine N-Methyltransferase

Topics

• Animals
• Chemokine CCL2 (metabolism)
• Diet, High-Fat (adverse effects, methods)
• Disease Models, Animal
• Fatty Liver (etiology, metabolism, pathology, physiopathology)
• Interleukin-10 (metabolism)
• Liver (innervation, metabolism, pathology)
• Mice
• Obesity
• Phosphatidylcholines (biosynthesis)
• Phosphatidylethanolamine N-Methyltransferase (metabolism)
• Postoperative Period
• Transcription Factor CHOP (metabolism)
• Vagotomy (adverse effects, methods)
• Vagus Nerve (physiopathology)