Neural Circuits Underlying Reciprocal Cardiometabolic Crosstalk: 2023 Arthur C. Corcoran Memorial Lecture

Hypertension, Год журнала: 2024, Номер 81(6), С. 1233 - 1243

Опубликована: Март 27, 2024

The interplay of various body systems, encompassing those that govern cardiovascular and metabolic functions, has evolved alongside the development multicellular organisms. This evolutionary process is essential for coordination maintenance homeostasis overall health by facilitating adaptation organism to internal external cues. Disruption these complex interactions contributes progression pathologies involve multiple organs. Obesity-associated risks, such as hypertension, highlight significant influence processes exert on system. cardiometabolic communication reciprocal, indicated substantial evidence pointing ability system affect processes, with pathophysiological implications in disease conditions. In this review, I outline bidirectional nature interaction, special emphasis impact organs have also discuss contribution neural circuits autonomic nervous mediating crosstalk between functions disease, along molecular mechanisms involved.

Язык: Английский

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

Опубликована: Май 7, 2024

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

Язык: Английский

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

Опубликована: Май 7, 2024

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

Язык: Английский

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Increased Heart Rate Fragmentation in Those with Williams-Beuren Syndrome Suggests Non-autonomic Mechanistic Contributors to Sudden Death Risk

AJP Heart and Circulatory Physiology, Год журнала: 2024, Номер 327(2), С. H521 - H532

Опубликована: Авг. 1, 2024

Williams-Beuren syndrome (WBS) is a rare genetic condition caused by chromosomal microdeletion at 7q11.23. It multisystem disorder characterized distinct facies, intellectual disability, and supravalvar aortic stenosis (SVAS). Those with WBS are increased risk of sudden death, but mechanisms underlying this remain poorly understood. We recently demonstrated autonomic abnormalities in those that associated susceptibility to arrhythmia cardiac death (SCD). A introduced method for heart rate variability (HRV) analysis called "heart fragmentation" (HRF) correlates adverse cardiovascular events (CVEs) studies where failed identify high-risk subjects. Some argue HRF quantifies nonautonomic modulators. We, therefore, sought apply cohort determine

Язык: Английский

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

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 13, 2023

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

Язык: Английский

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Chronic vagotomy induces nTS glial activation, reduced glutamatergic signaling, and blunted cardiorespiratory responses

Опубликована: Янв. 1, 2023

The brainstem nucleus tractus solitarii (nTS) is the first site of integration viscerosensory information provided by afferents vagus nerves. nTS critically contributes to cardiorespiratory function and displays remarkable neuroplasticity in response changes afferent input. Vagal form synapses with neurons that are closely associated astrocytes, forming tripartite synapse. We hypothesized reducing vagal input via chronic unilateral vagotomy would alter synapse nTS, resulting activity. In results Aim 1, we showed induced astrocyte reactivity microglial activation nTS. This corresponded a reduction augmented breaths (sighs) during hypoxia. 2, further investigated effects stimulating recording sympathetic responses. Blunted responses stimulation lead us hypothesize reactive astrocytes at may be contributing this through increased glutamate uptake. Instead found evidence reduced excitability vagotomized decreased postsynaptic NMDA receptor function, leading blunted neuronal upon stimulation. Together these demonstrate multiple occur following vagotomy, contribute reflex affect health disease.

Язык: Английский

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