Insights Into the Effects of Low-Level Vagus Nerve Stimulation on Atrial Electrophysiology

Kharbanda, Rohit K.; Misier, Nawin L. Ramdat; Schie, Mathijs S. van; Zwijnenburg, Roxanne D.; Amesz, Jorik H.; Knops, Paul; Bogers, Ad J.J.C.; Taverne, Yannick J.H.J.; Groot, Natasja M.S. de

doi:10.1016/j.jacep.2023.05.011

Cited by 3 publications

(2 citation statements)

References 29 publications

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“…Our findings provide new possible glucagon-related targets for treating obesity-associated cardiac arrhythmia by targeting cardiac neurons receptive to glucagon signaling rather than the cardiomyocytes as had been the leading hypothesis to date. Studies into the human equivalent of ACN would be interesting; possibly the vagus nerve could fulfill a similar function as its importance for cardiac rhythm has been firmly established (Ambache and Lippold, 1949; Cai et al, 2023; Freeman, 1951; González et al, 2023; Kharbanda et al, 2023; van Weperen and Vaseghi, 2023).…”

Section: Discussionmentioning

confidence: 99%

“…Given the conservation of Akh/glucagon signaling, these findings likely have implications for arrhythmia in patients. Given the significance of the vagus nerve in cardiac rhythm (Ambache and Lippold, 1949; Cai et al, 2023; Freeman, 1951; González et al, 2023; Kharbanda et al, 2023; van Weperen and Vaseghi, 2023) it could fulfill a similar function.…”

Section: Introductionmentioning

confidence: 99%

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Cardiac neurons expressing a glucagon-like receptor mediate cardiac arrhythmia induced by high-fat diet inDrosophila

Zhao,

Duan,

van de Leemput

et al. 2023

Preprint

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Cardiac arrhythmia leads to increased risks for stroke, heart failure, and cardiac arrest. Arrhythmic pathology is rooted in the cardiac conduction system, but the mechanism is complex and not fully understood. For example, how metabolic diseases, like obesity and diabetes, increase the risk for cardiac arrhythmia. Glucagon regulates glucose production, mobilizes lipids from the fat body, and affects cardiac rate and rhythm, attributes of a likely key player.Drosophilais an established model to study metabolic diseases and cardiac arrhythmias. Since glucagon signaling is highly conserved, we used high-fat diet (HFD)-fed flies to study its effect on heart function. HFD led to increased heartbeat and an irregular rhythm. The HFD-fed flies showed increased levels of adipokinetic hormone (Akh), the functional equivalent to human glucagon. Both genetic reduction of Akh and eliminating the Akh producing cells (APC) rescued HFD-induced arrhythmia, whereas heart rhythm was normal in Akh receptor mutants (AkhRnull). Furthermore, we discovered a pair of cardiac neurons that express high levels of Akh receptor. These are located near the posterior heart, make synaptic connections at the heart muscle, and regulate heart rhythm. Altogether, this Akh signaling pathway provides new understanding of the regulatory mechanisms between metabolic disease and cardiac arrhythmia.HIGHLIGHTSHigh-fat diet activates Akh (glucagon-like)-producing neurons near the esophagus inDrosophilaReducing Akh prevents high-fat diet-induced cardiac arrhythmia in fliesDiscovery of two neurons located at the posterior end of the heart that express the Akh receptor (AkhR) and innervate the heartEliminating one of the two AkhR-expressing cardiac neurons (ACN) results in cardiac arrhythmia, whereas the absence of functional AkhR prevents high-fat diet-induced cardiac arrhythmia in flies

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cardiac neurons expressing a glucagon-like receptor mediate cardiac arrhythmia induced by high-fat diet inDrosophila

Zhao,

Duan,

van de Leemput

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Cardiac neurons expressing a glucagon-like receptor mediate cardiac arrhythmia induced by high-fat diet in Drosophila

Zhao,

Duan,

van de Leemput

et al. 2024

Preprint

View full text Add to dashboard Cite

Cardiac arrhythmia leads to increased risks for stroke, heart failure, and cardiac arrest. Arrhythmic pathology is rooted in the cardiac conduction system, but the mechanism is complex and not fully understood. For example, how metabolic diseases, like obesity and diabetes, increase the risk for cardiac arrhythmia. Glucagon regulates glucose production, mobilizes lipids from the fat body, and affects cardiac rate and rhythm, attributes of a likely key player. Drosophila is an established model to study metabolic diseases and cardiac arrhythmias. Since glucagon signaling is highly conserved, we used high-fat diet (HFD)-fed flies to study its effect on heart function. HFD led to increased heartbeat and an irregular rhythm. The HFD-fed flies showed increased levels of adipokinetic hormone (Akh), the functional equivalent to human glucagon. Both genetic reduction of Akh and eliminating the Akh producing cells (APC) rescued HFD-induced arrhythmia, whereas heart rhythm was normal in Akh receptor mutants ( AkhR null ). Furthermore, we discovered a pair of cardiac neurons that express high levels of Akh receptor. These are located near the posterior heart, make synaptic connections at the heart muscle, and regulate heart rhythm. Altogether, this Akh signaling pathway provides new understanding of the regulatory mechanisms between metabolic disease and cardiac arrhythmia.

show abstract

Cardiac neurons expressing a glucagon-like receptor mediate cardiac arrhythmia induced by high-fat diet in Drosophila

Zhao,

Duan,

van de Leemput

et al. 2024

Preprint

View full text Add to dashboard Cite

Cardiac arrhythmia leads to increased risks for stroke, heart failure, and cardiac arrest. Arrhythmic pathology is rooted in the cardiac conduction system, but the mechanism is complex and not fully understood. For example, how metabolic diseases, like obesity and diabetes, increase the risk for cardiac arrhythmia. Glucagon regulates glucose production, mobilizes lipids from the fat body, and affects cardiac rate and rhythm, attributes of a likely key player. Drosophila is an established model to study metabolic diseases and cardiac arrhythmias. Since glucagon signaling is highly conserved, we used high-fat diet (HFD)-fed flies to study its effect on heart function. HFD led to increased heartbeat and an irregular rhythm. The HFD-fed flies showed increased levels of adipokinetic hormone (Akh), the functional equivalent to human glucagon. Both genetic reduction of Akh and eliminating the Akh producing cells (APC) rescued HFD-induced arrhythmia, whereas heart rhythm was normal in Akh receptor mutants ( AkhR null ). Furthermore, we discovered a pair of cardiac neurons that express high levels of Akh receptor. These are located near the posterior heart, make synaptic connections at the heart muscle, and regulate heart rhythm. Altogether, this Akh signaling pathway provides new understanding of the regulatory mechanisms between metabolic disease and cardiac arrhythmia.

show abstract

Insights Into the Effects of Low-Level Vagus Nerve Stimulation on Atrial Electrophysiology

Cited by 3 publications

References 29 publications

Cardiac neurons expressing a glucagon-like receptor mediate cardiac arrhythmia induced by high-fat diet inDrosophila

Cardiac neurons expressing a glucagon-like receptor mediate cardiac arrhythmia induced by high-fat diet inDrosophila

Cardiac neurons expressing a glucagon-like receptor mediate cardiac arrhythmia induced by high-fat diet in Drosophila

Cardiac neurons expressing a glucagon-like receptor mediate cardiac arrhythmia induced by high-fat diet in Drosophila

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