Early central cardiovagal dysfunction after high fat diet in a murine model

Area of Science:

• Cardiovascular Physiology
• Neuroscience
• Metabolic Disease Research

Background:

• High-fat diets (HFD) are linked to cardiovascular disease and reduced cardiac vagal regulation.
• The early onset and mechanisms of this vagal dysfunction remain unclear.

Purpose of the Study:

• To investigate the temporal onset of reduced central vagal regulation following HFD.
• To elucidate the underlying molecular mechanisms contributing to HFD-induced cardiac dysregulation.

Main Methods:

• Cardiovascular testing and pharmacology in mice.
• Molecular biology techniques to assess receptor expression.
• Utilized a novel bi-transgenic mouse line (ChAT-δ^null) lacking specific GABA receptor subunits in vagal motor neurons.

Main Results:

• HFD significantly blunted cardio/pulmonary chemoreflex bradycardic responses by 15 days, persisting beyond 30 days.
• Resting tachycardia, indicating parasympathetic tone loss, was observed by day 3 of HFD.
• Central mediation of vagal dysfunction was confirmed, with increased GABA_A(δ)R expression in the nucleus ambiguus (NA) at 15 days.
• ChAT-δ^null mice did not exhibit HFD-induced blunted reflex bradycardia or resting tachycardia.

Conclusions:

• Reduced parasympathetic output, likely mediated by increased GABA_A(δ)Rs in vagal motor neurons, contributes to early HFD-induced heart rate dysregulation.
• These findings highlight the need to investigate the mechanisms of early GABA_A(δ)R upregulation and subsequent parasympathetic dysfunction in HFD contexts.