1. High-Fat Diet Modulates the Excitability of Neurons within the Brain–Liver Pathway.
- Author
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Molinas, Adrien J. R., Desmoulins, Lucie D., Davis, Roslyn K., Gao, Hong, Satou, Ryousuke, Derbenev, Andrei V., and Zsombok, Andrea
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HYPOTHALAMUS ,HIGH-fat diet ,NEURONS ,SYMPATHETIC nervous system ,PARAVENTRICULAR nucleus ,INSULIN receptors - Abstract
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. [ABSTRACT FROM AUTHOR] more...
- Published
- 2023
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