Group on the Molecular and Cell Biology of Lipids, and Department of Biochemistry, University of Alberta, Edmonton, Canada.
Department of Surgery, University of Alberta, Edmonton, AB, Canada.
J Hepatol. 2015 Apr;62(4):913-20. doi: 10.1016/j.jhep.2014.11.026. Epub 2014 Nov 27.
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.
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.
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.
Neuronal signals via the hepatic vagus nerve contribute to the development of steatohepatitis and protection against obesity in HFD fed Pemt(-/-) mice.
磷酸乙醇胺 N-甲基转移酶（PEMT）是一种丰富于肝脏的酶，负责约三分之一的肝磷脂酰胆碱生物合成。高脂肪饮食（HFD）喂养的 Pemt（-/-）小鼠可免受 HF 诱导的肥胖，但会发展为脂肪性肝炎。迷走神经在肝脏和大脑之间传递信号，调节外周肥胖和胰腺功能。在这里，我们探讨了迷走神经肝支在 Pemt（-/-）小鼠饮食诱导肥胖和脂肪性肝炎发展中的可能作用。
8 周龄的 Pemt（-/-）和 Pemt（+/+）小鼠接受肝迷走神经切断术（HV）或辣椒素处理，分别选择性地破坏传入神经，并与假手术或载体处理相比较。手术后，小鼠喂食 HFD 10 周。
HV 消除了 Pemt（-/-）小鼠对 HFD 诱导的肥胖和葡萄糖不耐受的保护作用。HV 使 Pemt（-/-）小鼠的磷脂含量正常化并预防脂肪性肝炎。此外，HV 增加了肝脏抗炎细胞因子白细胞介素 10，减少了趋化因子单核细胞趋化蛋白-1 和 ER 应激标志物 C/EBP 同源蛋白。此外，HV 使 Pemt（-/-）小鼠的线粒体电子传递链蛋白和脂肪酸合成相关蛋白、乙酰辅酶 A 羧化酶和脂肪酸合酶的表达正常化。然而，辣椒素破坏肝传入迷走神经未能逆转 Pemt（-/-）小鼠对 HFD 诱导的肥胖的保护作用或 HF 诱导的脂肪性肝炎的发展。
通过肝迷走神经的神经元信号有助于 HFD 喂养的 Pemt（-/-）小鼠脂肪性肝炎的发展和肥胖的保护。
