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Free Fatty Acid Receptor G-protein-coupled Receptor 40 Mediates Lipid Emulsion-induced Cardioprotection
Soban Umar1, Jingyuan Li, Kyle Hannabass
1From the Department of Anesthesiology and Perioperative Medicine, Division of Molecular Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California.
Anesthesiology
|April 6, 2018
Summary
Lipid emulsion protects the heart from injury by activating G-protein-coupled receptor 40 (GPCR40). Blocking GPCR40 with GW1100 negates this protective effect in ischemia/reperfusion and bupivacaine toxicity models.
Area of Science:
- Cardiology
- Pharmacology
- Molecular Biology
Background:
- Intralipid (lipid emulsion) is known to protect the heart from ischemia/reperfusion (I/R) injury and bupivacaine cardiotoxicity.
- The exact mechanisms underlying lipid emulsion's cardioprotective effects remain unclear.
- This study investigates the role of free fatty acid receptor-1 (FFAR1), also known as G-protein-coupled receptor 40 (GPCR40), in mediating these protective effects.
Purpose of the Study:
- To determine if GPCR40 is expressed in the heart.
- To test the hypothesis that lipid emulsion's cardioprotective effects are mediated through GPCR40.
- To evaluate GPCR40's involvement in models of I/R injury and bupivacaine-induced cardiotoxicity.
Main Methods:
- Langendorff-perfused mouse hearts underwent I/R with lipid emulsion or lipid emulsion plus a GPCR40 antagonist (GW1100).
- Male rats received bupivacaine to induce cardiotoxicity, followed by lipid emulsion or GW1100 pretreatment before lipid emulsion.
- Cardiac function parameters such as rate pressure product, left ventricular developed pressure, and ejection fraction were measured.
Main Results:
- GPCR40 is expressed in rodent hearts.
- GW1100 significantly abolished the cardioprotective effects of lipid emulsion against I/R injury in mice.
- In the bupivacaine model, GW1100 pretreatment prevented the beneficial effects of lipid emulsion on heart rate and ejection fraction.
Conclusions:
- G-protein-coupled receptor 40 is expressed in the rodent heart.
- GPCR40 plays a crucial role in the cardioprotection afforded by lipid emulsion against both ischemia/reperfusion injury and bupivacaine-induced cardiotoxicity.
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