Xia Gao1, Jelske N van der Veen1, Linfu Zhu2, Todd Chaba3, Marta Ordoñez4, Susanne Lingrell1, Debby P Y Koonen5, Jason R B Dyck6, Antonio Gomez-Muñoz4, Dennis E Vance1, René L Jacobs7. 1. Group on the Molecular and Cell Biology of Lipids, and Department of Biochemistry, University of Alberta, Edmonton, Canada. 2. Department of Surgery, University of Alberta, Edmonton, AB, Canada. 3. Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada. 4. Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Bilbao, Spain. 5. Department of Pediatrics, Section Molecular Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 6. Cardiovascular Research Centre and Department of Pediatrics, University of Alberta, Edmonton, Canada. 7. Group on the Molecular and Cell Biology of Lipids, and Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, Canada. Electronic address: rjacobs@ualberta.ca.
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.
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; Carlos Fernandez-Patron; Jean E Vance; Dennis E Vance; René L Jacobs Journal: J Lipid Res Date: 2015-06-25 Impact factor: 5.922
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Authors: Yuan Zhang; Jason D Kang; Derrick Zhao; Siddartha S Ghosh; Yanyan Wang; Yunling Tai; Javier Gonzalez-Maeso; Masoumeh Sikaroodi; Patrick M Gillevet; H Robert Lippman; Phillip B Hylemon; Huiping Zhou; Jasmohan S Bajaj Journal: Front Physiol Date: 2021-06-25 Impact factor: 4.566