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Published on: August 14, 2013
Effects of Incretin-Based Therapies on Neuro-Cardiovascular Dynamic Changes Induced by High Fat Diet in Rats
Silvio Rodrigues Marques-Neto1, Raquel Carvalho Castiglione1, Aiza Pontes1
1Laboratory for Clinical and Experimental Research on Vascular Biology (BioVasc), Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Background And Aims:
Obesity promotes cardiac and cerebral microcirculatory dysfunction that could be improved by incretin-based therapies. However, the effects of this class of compounds on neuro-cardiovascular system damage induced by high fat diet remain unclear. The aim of this study was to investigate the effects of incretin-based therapies on neuro-cardiovascular dysfunction induced by high fat diet in Wistar rats.
Methods And Results:
We have evaluated fasting glucose levels and insulin resistance, heart rate variability quantified on time and frequency domains, cerebral microcirculation by intravital microscopy, mean arterial blood pressure, ventricular function and mitochondrial swelling. High fat diet worsened biometric and metabolic parameters and promoted deleterious effects on autonomic, myocardial and haemodynamic parameters, decreased capillary diameters and increased functional capillary density in the brain. Biometric and metabolic parameters were better improved by glucagon like peptide-1 (GLP-1) compared with dipeptdyl peptidase-4 (DPP-4) inhibitor. On the other hand, both GLP-1 agonist and DPP-4 inhibitor reversed the deleterious effects of high fat diet on autonomic, myocardial, haemodynamic and cerebral microvascular parameters. GLP-1 agonist and DPP-4 inhibitor therapy also increased mitochondrial permeability transition pore resistance in brain and heart tissues of rats subjected to high fat diet.
Conclusion:
Incretin-based therapies improve deleterious cardiovascular effects induced by high fat diet and may have important contributions on the interplay between neuro-cardiovascular dynamic controls through mitochondrial dysfunction associated to metabolic disorders.
Insights
Incretin-based therapies, including glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, effectively reversed high-fat diet-induced neuro-cardiovascular damage in rats. These treatments improved autonomic, cardiac, and cerebral microvascular functions by targeting mitochondrial dysfunction.
Area of Science:
- Cardiovascular Science
- Metabolic Disorders
- Neuroscience
Background:
- Obesity exacerbates cardiac and cerebral microcirculatory dysfunction.
- Incretin-based therapies show potential for improving these conditions.
- The specific impact of incretin-based therapies on high-fat diet-induced neuro-cardiovascular damage requires clarification.
Purpose of the Study:
- To investigate the effects of incretin-based therapies on neuro-cardiovascular dysfunction induced by a high-fat diet in Wistar rats.
Main Methods:
- Evaluated fasting glucose, insulin resistance, heart rate variability, cerebral microcirculation, arterial blood pressure, ventricular function, and mitochondrial swelling.
- Compared the efficacy of glucagon-like peptide-1 (GLP-1) agonist versus dipeptidyl peptidase-4 (DPP-4) inhibitor.
- Assessed changes in brain and heart tissues.
Main Results:
- High-fat diet impaired metabolic, autonomic, myocardial, hemodynamic, and cerebral microvascular parameters.
- Both GLP-1 agonist and DPP-4 inhibitor treatments reversed these detrimental effects.
- GLP-1 showed superior improvement in metabolic parameters compared to DPP-4 inhibitor.
- Therapies enhanced mitochondrial permeability transition pore resistance in brain and heart.
Conclusions:
- Incretin-based therapies effectively mitigate high-fat diet-induced cardiovascular damage.
- These therapies positively influence neuro-cardiovascular dynamics.
- Mitochondrial dysfunction plays a key role in metabolic disorders and associated neuro-cardiovascular damage.
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