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Author Spotlight: Unveiling Mitochondrial Function and Cellular Metabolic Adaptation in Metabolic Diseases
Published on: October 4, 2024
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A gut microbiome metabolite paradoxically depresses contractile function while activating mitochondrial respiration
Saba Naghipour1, Joshua J Fisher2, Anthony V Perkins1
1School of Pharmacy and Medical Science, Griffith University, Southport, QLD 4215, Australia.
Disease Models & Mechanisms
|April 20, 2023
Summary
Trimethylamine-N-oxide (TMAO), a gut microbe product, impairs heart contractility and constricts coronary arteries at levels seen in advanced cardiovascular disease (CVD). Paradoxically, it boosts mitochondrial respiration.
Area of Science:
- Cardiovascular Physiology
- Metabolic Biochemistry
- Gut Microbiome Research
Background:
- Trimethylamine-N-oxide (TMAO) is a metabolite linked to cardiovascular disease (CVD) risk.
- The specific acute cardiovascular effects of TMAO at disease-relevant concentrations are not fully understood.
Purpose of the Study:
- To investigate the acute effects of TMAO on cardiac contractile function, coronary blood flow, and mitochondrial respiration.
- To determine the concentration-dependent impact of TMAO on isolated mouse hearts.
Main Methods:
- Langendorff perfusion of male C57Bl/6 mouse hearts.
- Assessment of left ventricular (LV) function and coronary flow across a range of TMAO concentrations (1-300 µM).
- Mitochondrial respirometry and protein expression analysis.
Main Results:
- TMAO (10-300 µM) concentration-dependently reduced LV contractile function and coronary flow.
- TMAO (>30 µM) induced coronary constriction, though attenuated.
- TMAO (10-100 µM) enhanced mitochondrial respiration (complex I, II, maximal fluxes) but potentially compromised outer membrane integrity.
- Reduced expression of phosphorylated AMPKα and total GSK-3β was observed.
Conclusions:
- Acute exposure to TMAO at levels found in advanced CVD inhibits cardiac contractility and causes coronary constriction.
- TMAO paradoxically increases mitochondrial respiration despite negative cardiac effects.
- Further research is needed to elucidate TMAO's complex role in cardiovascular pathophysiology.
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