High-Fat Diet Modulates the Excitability of Neurons within the Brain–Liver Pathway
Stimulation of hepatic sympathetic nerves increases glucose production and glycogenolysis. Activity of pre-sympathetic neurons in the paraventricular nucleus (PVN) of the hypothalamus and in the ventrolateral and ventromedial medulla (VLM/VMM) largely influence the sympathetic output. Increased acti...
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MDPI AG
2023-04-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/8/1194 |
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| author | Adrien J. R. Molinas Lucie D. Desmoulins Roslyn K. Davis Hong Gao Ryousuke Satou Andrei V. Derbenev Andrea Zsombok |
| author_facet | Adrien J. R. Molinas Lucie D. Desmoulins Roslyn K. Davis Hong Gao Ryousuke Satou Andrei V. Derbenev Andrea Zsombok |
| author_sort | Adrien J. R. Molinas |
| collection | DOAJ |
| description | Stimulation of hepatic sympathetic nerves increases glucose production and glycogenolysis. Activity of pre-sympathetic neurons in the paraventricular nucleus (PVN) of the hypothalamus and in the ventrolateral and ventromedial medulla (VLM/VMM) largely influence the sympathetic output. Increased activity of the sympathetic nervous system (SNS) plays a role in the development and progression of metabolic diseases; however, despite the importance of the central circuits, the excitability of pre-sympathetic liver-related neurons remains to be determined. Here, we tested the hypothesis that the activity of liver-related neurons in the PVN and VLM/VMM is altered in diet-induced obese mice, as well as their response to insulin. Patch-clamp recordings were conducted from liver-related PVN neurons, VLM-projecting PVN neurons, and pre-sympathetic liver-related neurons in the ventral brainstem. Our data demonstrate that the excitability of liver-related PVN neurons increased in high-fat diet (HFD)-fed mice compared to mice fed with control diet. Insulin receptor expression was detected in a population of liver-related neurons, and insulin suppressed the firing activity of liver-related PVN and pre-sympathetic VLM/VMM neurons in HFD mice; however, it did not affect VLM-projecting liver-related PVN neurons. These findings further suggest that HFD alters the excitability of pre-autonomic neurons as well as their response to insulin. |
| first_indexed | 2024-03-11T05:08:48Z |
| format | Article |
| id | doaj.art-28f6ae5c109b4a2db72485860ddc1e8f |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T05:08:48Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-28f6ae5c109b4a2db72485860ddc1e8f2023-11-17T18:43:49ZengMDPI AGCells2073-44092023-04-01128119410.3390/cells12081194High-Fat Diet Modulates the Excitability of Neurons within the Brain–Liver PathwayAdrien J. R. Molinas0Lucie D. Desmoulins1Roslyn K. Davis2Hong Gao3Ryousuke Satou4Andrei V. Derbenev5Andrea Zsombok6Department of Physiology, School of Medicine, Tulane University, New Orleans, LA 70130, USADepartment of Physiology, School of Medicine, Tulane University, New Orleans, LA 70130, USADepartment of Physiology, School of Medicine, Tulane University, New Orleans, LA 70130, USADepartment of Physiology, School of Medicine, Tulane University, New Orleans, LA 70130, USADepartment of Physiology, School of Medicine, Tulane University, New Orleans, LA 70130, USADepartment of Physiology, School of Medicine, Tulane University, New Orleans, LA 70130, USADepartment of Physiology, School of Medicine, Tulane University, New Orleans, LA 70130, USAStimulation of hepatic sympathetic nerves increases glucose production and glycogenolysis. Activity of pre-sympathetic neurons in the paraventricular nucleus (PVN) of the hypothalamus and in the ventrolateral and ventromedial medulla (VLM/VMM) largely influence the sympathetic output. Increased activity of the sympathetic nervous system (SNS) plays a role in the development and progression of metabolic diseases; however, despite the importance of the central circuits, the excitability of pre-sympathetic liver-related neurons remains to be determined. Here, we tested the hypothesis that the activity of liver-related neurons in the PVN and VLM/VMM is altered in diet-induced obese mice, as well as their response to insulin. Patch-clamp recordings were conducted from liver-related PVN neurons, VLM-projecting PVN neurons, and pre-sympathetic liver-related neurons in the ventral brainstem. Our data demonstrate that the excitability of liver-related PVN neurons increased in high-fat diet (HFD)-fed mice compared to mice fed with control diet. Insulin receptor expression was detected in a population of liver-related neurons, and insulin suppressed the firing activity of liver-related PVN and pre-sympathetic VLM/VMM neurons in HFD mice; however, it did not affect VLM-projecting liver-related PVN neurons. These findings further suggest that HFD alters the excitability of pre-autonomic neurons as well as their response to insulin.https://www.mdpi.com/2073-4409/12/8/1194paraventricular nucleusventral brainstemsympathetic nervous systempseudorabies virusliverhigh-fat diet |
| spellingShingle | Adrien J. R. Molinas Lucie D. Desmoulins Roslyn K. Davis Hong Gao Ryousuke Satou Andrei V. Derbenev Andrea Zsombok High-Fat Diet Modulates the Excitability of Neurons within the Brain–Liver Pathway Cells paraventricular nucleus ventral brainstem sympathetic nervous system pseudorabies virus liver high-fat diet |
| title | High-Fat Diet Modulates the Excitability of Neurons within the Brain–Liver Pathway |
| title_full | High-Fat Diet Modulates the Excitability of Neurons within the Brain–Liver Pathway |
| title_fullStr | High-Fat Diet Modulates the Excitability of Neurons within the Brain–Liver Pathway |
| title_full_unstemmed | High-Fat Diet Modulates the Excitability of Neurons within the Brain–Liver Pathway |
| title_short | High-Fat Diet Modulates the Excitability of Neurons within the Brain–Liver Pathway |
| title_sort | high fat diet modulates the excitability of neurons within the brain liver pathway |
| topic | paraventricular nucleus ventral brainstem sympathetic nervous system pseudorabies virus liver high-fat diet |
| url | https://www.mdpi.com/2073-4409/12/8/1194 |
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