High-Fat Diet Modulates the Excitability of Neurons within the Brain-Liver Pathway

• Published in: Cells (Basel, Switzerland) Vol. 12; no. 8; p. 1194
• Main Authors: Molinas, Adrien J R, Desmoulins, Lucie D, Davis, Roslyn K, Gao, Hong, Satou, Ryousuke, Derbenev, Andrei V, Zsombok, Andrea
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.04.2023; MDPI
• Subjects: Animals; Autonomic nervous system; Brain; Brain research; Brain stem; Diet; Diet, High-Fat; Excitability; Firing pattern; Gene expression; Glucose; Health aspects; High fat diet; Homeostasis; Hyperglycemia; Hypothalamus; Injections; Insulin; Insulins - metabolism; Laboratory animals; Liver; Medulla oblongata; Metabolic disorders; Metabolism; Mice; Nervous system; Neurons; Neurons - metabolism; Paraventricular nucleus; pseudorabies virus; Sympathetic nerves; Sympathetic nervous system; ventral brainstem; United States; United States > US; ventral brainstem; patch-clamp electrophysiology; liver; pseudorabies virus; sympathetic nervous system; high-fat diet; brain–liver pathway; paraventricular nucleus
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12081194

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.